S. Nalamachu, J. Pergolizzi, R. Taylor, J. L. Quang, R. Raffa
Opioids are a treatment option for a variety of chronic pain conditions. But long-term opioid use can be associated with side effects, including hypogonadism. Opioid-induced hypogonadism (OIhG) is associated with the alteration of the hypothalamic-pituitary-gonadal axis (HPG). In males, hypogonadism can result in erectile dysfunction, reduced libido, fatigue, worsening mood, and increased risk of osteoporosis; in females, it can result in changes in the menstrual cycle and reduced libido, among other effects. A current treatment option for these patients is hormone replacement therapy. In this report, we discuss the problem of opioid-induced hypogonadism, and the therapeutic approach and the potential complications of treating pain patients using hormone replacement therapy.
{"title":"Hormone Replacement Therapy for Restoring the HPG Axis in Pain Patients Treated with Long-Term Opioid Analgesics","authors":"S. Nalamachu, J. Pergolizzi, R. Taylor, J. L. Quang, R. Raffa","doi":"10.4236/pp.2018.911036","DOIUrl":"https://doi.org/10.4236/pp.2018.911036","url":null,"abstract":"Opioids are a treatment option for a variety of chronic pain conditions. But long-term opioid use can be associated with side effects, including hypogonadism. Opioid-induced hypogonadism (OIhG) is associated with the alteration of the hypothalamic-pituitary-gonadal axis (HPG). In males, hypogonadism can result in erectile dysfunction, reduced libido, fatigue, worsening mood, and increased risk of osteoporosis; in females, it can result in changes in the menstrual cycle and reduced libido, among other effects. A current treatment option for these patients is hormone replacement therapy. In this report, we discuss the problem of opioid-induced hypogonadism, and the therapeutic approach and the potential complications of treating pain patients using hormone replacement therapy.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78272064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Due to the relatively high renal toxicity of vancomycin injection (VCM), setting an initial dose that achieves a trough that ranges between 10 and 20 μg/mL on day 3 is important to ensure safety and minimize side-effects, especially for patients with low renal function. To address these issues, the revised 2016 Therapeutic Drug Monitoring (TDM) Guidelines for Antimicrobial Agents (GL2016) proposed the use of a renal function-based, estimate glomerular filtration rate (eGFR) nomogram for setting the dose of VCM in Japan. Methods: Our hospital introduced the use of the GL2016 in September 2016 for the patients administered VCM. After setting the initial VCM dose using 1) a conventional VCM analysis software and 2) the GL2016 eGFR nomogram, the measured trough values on day 3 were compared and evaluated in this study. Results: With the VCM analysis software, the mean measured trough value in the a-total group (n = 53) was 12.8 ± 4.7 μg/mL. With the eGFR nomogram, the mean measured trough value in the b-total group (n = 13) was 9.6 ± 4.6 μg/mL. However, when the different severities of renal function were compared, the mean measured trough value was more significantly lower in the b-1 group than in the a-1 group among subjects with G2 and above (eGFR ≥ 60 mL/min/1.73 m2), but it was similar between the a-2 group and the b-2 group among subjects with G3 and below (eGFR 60 mL/min/1.73 m2). The proportion of subjects reaching the various trough ranges shows similar tendency. Conclusions: These data suggested that the measured trough value on day 3 was generally lower when the initial dose was established using the eGFR nomogram based on the GL2016, and this was especially prominent among patients with normal renal function. As for subjects with low renal function, the trough values were relatively high while ensuring safety.
{"title":"Comparison of Measured Trough Values after Deriving the Initial Dose Setting of Vancomycin with a Conventional Computer Software and a Nomogram Based on the Revised Japanese 2016 Therapeutic Drug Monitoring Guidelines for Antimicrobial Agents","authors":"Yasuhiro Kamioka, Hitoshi Suzuki, M. Seki, Ryusuke Ouchi, Shota Kashiwagura, Satoshi Koshika, Yoshiteru Watanabe","doi":"10.4236/PP.2018.911037","DOIUrl":"https://doi.org/10.4236/PP.2018.911037","url":null,"abstract":"Background: Due to the relatively high \u0000renal toxicity of vancomycin injection (VCM), setting an initial dose that \u0000achieves a trough that ranges between 10 and \u000020 μg/mL on day 3 is important to ensure safety and minimize side-effects, especially \u0000for patients with low renal function. To address these issues, the revised 2016 Therapeutic Drug Monitoring \u0000(TDM) Guidelines for Antimicrobial Agents (GL2016) proposed the use of a renal \u0000function-based, estimate glomerular filtration rate (eGFR) nomogram for setting \u0000the dose of VCM in Japan. Methods: Our hospital introduced the use of the GL2016 in September 2016 for the \u0000patients administered VCM. After setting the initial VCM dose using 1) a conventional VCM analysis software and 2) the GL2016 eGFR nomogram, the measured trough values on day 3 were \u0000compared and evaluated in this study. Results: \u0000With the VCM analysis software, the mean measured trough value in the a-total group (n = 53) was 12.8 ± 4.7 \u0000μg/mL. With the eGFR nomogram, the mean measured trough value in the b-total \u0000group (n = 13) was 9.6 ± 4.6 μg/mL. However, when the different severities of \u0000renal function were compared, the mean measured trough value was more \u0000significantly lower in the b-1 group than in the a-1 group among subjects with \u0000G2 and above (eGFR ≥ 60 mL/min/1.73 m2), \u0000but it was similar between the a-2 group and the b-2 group among subjects with \u0000G3 and below (eGFR 60 mL/min/1.73 m2). \u0000The proportion of subjects reaching the various trough ranges shows similar \u0000tendency. Conclusions: These \u0000data suggested that the measured trough value on day 3 was generally lower when \u0000the initial dose was established using the eGFR nomogram based on the GL2016, \u0000and this was especially prominent among patients with normal renal function. As \u0000for subjects with low renal function, the trough values were relatively high \u0000while ensuring safety.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88531847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The first “deuterated” drug has recently been approved by the U.S. FDA (Food & Drug Administration). A “deuterated” drug is a drug in which the hydrogen atom in one or more of the carbon-hydrogen bonds in its chemical structure is replaced by deuterium (“heavy hydrogen”, a hydrogen isotope that has a neutron, i.e., one neutron instead of the usual no neutrons). A carbon-deuterium (C-D) bond is more stable in the body than a carbon-hydrogen (C-H) bond. If the deuterium is strategically located in a drug’s chemical structure, the extra stability of the bond will be more resistant to metabolic breakdown, and the duration of drug action will be prolonged. We review the general concept of deuterated drugs, historical examples of the classes of application, and the new approval.
{"title":"The First Approved “Deuterated” Drug: A Short Review of the Concept","authors":"R. Raffa, J. Pergolizzi, R. Taylor","doi":"10.4236/PP.2018.910033","DOIUrl":"https://doi.org/10.4236/PP.2018.910033","url":null,"abstract":"The first “deuterated” drug has recently been approved by the U.S. FDA (Food & Drug Administration). A “deuterated” drug is a drug in which the hydrogen atom in one or more of the carbon-hydrogen bonds in its chemical structure is replaced by deuterium (“heavy hydrogen”, a hydrogen isotope that has a neutron, i.e., one neutron instead of the usual no neutrons). A carbon-deuterium (C-D) bond is more stable in the body than a carbon-hydrogen (C-H) bond. If the deuterium is strategically located in a drug’s chemical structure, the extra stability of the bond will be more resistant to metabolic breakdown, and the duration of drug action will be prolonged. We review the general concept of deuterated drugs, historical examples of the classes of application, and the new approval.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85109987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sumiyo Umeda, H. Yanaguimoto, Seiichi Furuta, N. Kurosawa
We surveyed the drug information retrieval practices among community pharmacists in more rural Hokkaido and in entire Japan in order to explore local characteristics of work-related issues, how community pharmacists access information to address such issues, and with whom they consult to solve them. Based on the findings, we propose a strategy for improvements in similar support systems. The percentage of respondents who had experience with home care services was significantly lower in the Hokkaido group (56.0% of 207) than in the nationwide group (70.0% of 250), as was the percentage of respondents who consulted the pharmacist association and branch board (13.0% and 20.4%, respectively). The Hokkaido group also made significantly less use of websites such as d.m3.com and e.CareNet.com. The results of this survey thus indicate that the drug information retrieval in the Hokkaido group had a low implementation rate of home care services. In addition, there were low levels of utilization of the local pharmacist association, and low utilization of the websites d.m3.com and e.CareNet.com. To enhance the Hokkaido community-based integrated care system (and ones like it), we propose that it is necessary to: 1) support activities of local pharmacist associations, and 2) promote proactive implementation of drug information retrieval through education.
{"title":"A Survey of Community Pharmacists about Work-Related Issues, How they Solve them, and who they Consult with to Solve them: Comparison of Results from the Hokkaido Area vs. a Nationwide Survey","authors":"Sumiyo Umeda, H. Yanaguimoto, Seiichi Furuta, N. Kurosawa","doi":"10.4236/pp.2018.910034","DOIUrl":"https://doi.org/10.4236/pp.2018.910034","url":null,"abstract":"We surveyed the drug information retrieval practices \u0000among community pharmacists in more rural Hokkaido and in entire Japan in order \u0000to explore local characteristics of work-related issues, how community pharmacists access information to address such issues, and with whom they consult to \u0000solve them. Based on the findings, we propose a strategy for improvements in similar support systems. The percentage of respondents who had experience with home care services was significantly \u0000lower in the Hokkaido group (56.0% of 207) than in the nationwide group (70.0% \u0000of 250), as was the percentage of respondents who consulted the pharmacist association and branch board \u0000(13.0% and 20.4%, respectively). The Hokkaido group also made significantly \u0000less use of websites such as d.m3.com and e.CareNet.com. The results of this \u0000survey thus indicate that the drug information retrieval in the Hokkaido group \u0000had a low implementation rate of home care services. In addition, there were \u0000low levels of utilization of the local pharmacist association, and low \u0000utilization of the websites d.m3.com and e.CareNet.com. To enhance the Hokkaido \u0000community-based integrated care system (and ones like it), we propose that it \u0000is necessary to: 1) support activities of local pharmacist associations, and 2) \u0000promote proactive implementation of drug information retrieval through \u0000education.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80949243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Sukoyan, Edisher E. Tsivtsivadze, V. V. Golovach, T. Kezeli, N. Demina
The aim of the study was to evaluate the efficacy of 2% Cynara scolymus L. extracts in reverse disturbances of collagen metabolism and inflammation in D-galactose induced skin aging model in rats. D-galactose induced aging reproduced in 48 animals of main group, and 12 rats in control group. All animals in main group were randomized for 4 groups: I. aging + saline, II - IV. different manufacturers 2% artichoke extracts (with content of chlorogenic acid 2.5%) in a dose of intradermal injection 0.13 mg twice at weeks during 4 weeks. Influence of artichoke extracts restored skin relative weight and led to an increase of solubility in neutral salt and acid, and decreased pepsin solubility collagen fraction, restored the hexosamine/collagen (hydroxyproline) ratio and decreased the activity of nuclear transcription factor (NF-kB). Local prolonged treatment with artichoke extracts improved collagen metabolism and attenuated the progression of inflammation in D-galactose induced skin aging model.
{"title":"Anti-Aging Effect of Cynara cardunculus L. var. Cynara scolymus L. Extract in D-Galactose-Induced Skin Aging Model in Rats","authors":"G. Sukoyan, Edisher E. Tsivtsivadze, V. V. Golovach, T. Kezeli, N. Demina","doi":"10.4236/PP.2018.910032","DOIUrl":"https://doi.org/10.4236/PP.2018.910032","url":null,"abstract":"The aim of the study was to evaluate the efficacy of \u00002% Cynara scolymus L. extracts in reverse disturbances of collagen \u0000metabolism and inflammation in D-galactose induced skin aging model in rats. \u0000D-galactose induced aging reproduced in 48 animals of main group, and 12 rats \u0000in control group. All animals in main group were randomized for 4 groups: I. aging + saline, II - IV. different manufacturers 2% artichoke extracts (with content of chlorogenic \u0000acid 2.5%) in a dose of intradermal injection 0.13 mg twice at weeks during 4 \u0000weeks. Influence of artichoke extracts restored skin relative weight and led to \u0000an increase of solubility in neutral salt and acid, and decreased pepsin solubility collagen fraction, restored the \u0000hexosamine/collagen (hydroxyproline) ratio and decreased the activity of \u0000nuclear transcription factor (NF-kB). Local prolonged treatment with artichoke \u0000extracts improved collagen metabolism and attenuated the progression of \u0000inflammation in D-galactose induced skin aging model.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89468196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. F. Bend, P. O. Oundoum, M. N. Njila, B. L. Koloko, Camille D. Nyonseu, S. Mandengue, P. Moundipa, T. Dimo, D. Lembè
The aim of the study was to bring scientific evidence of the curative action of the stem bark aqueous extract of Schumanniophyton magnificum (ASMa) on the sexual maturation and fertility of the immature female Wistar rat. Forty immature female rats were randomized and divided into 4 groups of ten animals each and orally treated with the ASMa at doses of 0 (distilled water), 200 mg/kg, 400 mg/kg and 800 mg/kg /BW/day for 30 consecutive days. Body weight and food intake were recorded throughout the experimental period. The precocity of the puberty onset in treated animals was evaluated through the determination of their age at vaginal opening. At the end of the experimental period, 5 animals in each group were sacrificed and blood samples were collected for hormonal assay. Their ovaries and uteri were removed, blotted, weighted and prepared for biochemical analysis. The remaining rats (5 per group) were crossed with males of proven fertility. After laparotomy (ten days after mating) and delivery, fertility and gestational parameters were recorded. It was noticed that, body weight gain increased significantly at all doses although there was no significant difference in food intake. The sexual maturation of treated animal was reduced to 5 days when compared to control. This was associated with the simultaneous elevation of FSH and LH (p mg/kg. However, the ovarian cholesterol significantly decreased (p mg/kg and 800 mg/kg. The animal treated at doses of 400 mg/kg and 800 mg/kg exhibited an early fertilization (2 - 3 days) when compared to the control one (9 - 14 days). The number of implantation site significantly increased (p mg/kg and 800 mg/kg) after laparotomy as well as the number of alive fetuses after delivery and gestational rate (80% and 100%) respectively. These results provide the strong evidence on the induction of the onset puberty and gonadotropin synthesis, the improvement of the ovarian folliculogenesis and the fertility effect of ASMa in immature rats.
{"title":"Effect of the Aqueous Extract of Schumanniophyton magnificum Harms on Sexual Maturation and Fertility of Immature (K. schum) Female Rat","authors":"E. F. Bend, P. O. Oundoum, M. N. Njila, B. L. Koloko, Camille D. Nyonseu, S. Mandengue, P. Moundipa, T. Dimo, D. Lembè","doi":"10.4236/pp.2018.910031","DOIUrl":"https://doi.org/10.4236/pp.2018.910031","url":null,"abstract":"The aim of the study was to bring scientific \u0000evidence of the curative action of the stem bark aqueous extract of Schumanniophyton \u0000magnificum (ASMa) on the sexual maturation and fertility of the immature \u0000female Wistar rat. Forty immature female rats were randomized and divided into \u00004 groups of ten animals each and orally treated with the ASMa at doses of 0 \u0000(distilled water), 200 mg/kg, 400 mg/kg and 800 mg/kg /BW/day for 30 consecutive days. Body weight and food intake were \u0000recorded throughout the experimental period. The precocity of the puberty onset \u0000in treated animals was evaluated through the determination of their age at \u0000vaginal opening. At the end of the experimental period, 5 animals in each group \u0000were sacrificed and blood samples were collected for hormonal assay. Their \u0000ovaries and uteri were removed, blotted, weighted and prepared for biochemical analysis. \u0000The remaining rats (5 per group) were crossed with males of proven fertility. \u0000After laparotomy (ten days after mating) and delivery, fertility and \u0000gestational parameters were recorded. It was noticed that, body weight gain \u0000increased significantly at all doses although there was no significant difference in food intake. The sexual maturation of \u0000treated animal was reduced to 5 days when compared to control. This was \u0000associated with the simultaneous elevation of FSH and LH (p mg/kg. However, the ovarian cholesterol significantly decreased (p mg/kg and 800 mg/kg. The animal treated at \u0000doses of 400 mg/kg and 800 mg/kg exhibited an early fertilization (2 - 3 days) when compared to the control one (9 - 14 days). The number of implantation site significantly increased (p mg/kg and 800 mg/kg) after laparotomy as \u0000well as the number of alive fetuses after delivery and gestational rate (80% \u0000and 100%) respectively. These results provide the strong evidence on the \u0000induction of the onset puberty and gonadotropin synthesis, the improvement of \u0000the ovarian folliculogenesis and the fertility effect of ASMa in immature rats.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90378525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sabarni Sarker, Md. Ashraf Ali, R. Barman, Shuji Noguchi, Y. Iwao, S. Itai, M. I. I. Wahed
The use of Nifedipine (NI), a dihydropyridine calcium channel blocker, is limited due to its poor aqueous solubility. However, NI loaded solid-lipid nanoparticles (NI-SLN) are known to exhibit suitable pharmacokinetic properties and good biocompatibility. The present investigation was designed to evaluate the effects of NI-SLN on glucose homeostasis, lipid metabolism and liver function in fructose-induced diabetic rats. NI-SLN was prepared by high pressure homogenization technique followed by lyophilization with trehalose as cryoprotectant. Diabetes was induced into rats by the administration of fructose (10%) in drinking water for six weeks. After induction of diabetes, rats were divided into four groups for the oral ingestion of NI, NI-SLN and/or vehicles and their effects on blood glucose levels, oral glucose tolerance test (OGTT), lipid profile, biochemical parameters, electrolytes and histopathology were observed. Single dose administration and treatment with NI-SLN showed significant glucose lowering efficacy in fructose-induced diabetic rats. Although NI and NI-SLN did not alter the fasting blood glucose level in normal rats, diabetic rats treated with NI-SLN resulted in significant reduction in glucose level for 24 hr. In OGTT, NI-SLN exhibited significant antihyperglycemic activity in both normal and diabetic rats. So, NI-SLN has better glucose lowering efficacy than that of pure NI in diabetic rats. The survival rates in rats among the treatment groups were 100%. Treatment with NI-SLN significantly improved lipid profiles than NI alone and the effect was dose-dependent. Administration of NI-SLN significantly reduced uric acid, creatinine levels and maintained a good cationic balance. After two weeks of NI-SLN treatment, hepatocytes regained their normal architecture, and the beneficial effect could be correlated with the reduction of SGOT and total bilirubin levels. Therefore, NI-SLN was found to be useful for the enhancement of bioavailability and exhibited profound antidiabetic activity in rats. The results of the study suggested that NI-SLN exerted better improvement in glucose levels, lipid profiles and organ protection than pure NI and might have some beneficial effects in the management of diabetic patients.
{"title":"Preparation and Antidiabetic Effect of Orally Administered Nifedipine‐Loaded Solid Lipid Nanoparticles in Fructose-Induced Diabetic Rats","authors":"Sabarni Sarker, Md. Ashraf Ali, R. Barman, Shuji Noguchi, Y. Iwao, S. Itai, M. I. I. Wahed","doi":"10.4236/PP.2018.910035","DOIUrl":"https://doi.org/10.4236/PP.2018.910035","url":null,"abstract":"The use of Nifedipine (NI), a dihydropyridine \u0000calcium channel blocker, is limited due to its \u0000poor aqueous solubility. However, NI loaded solid-lipid nanoparticles (NI-SLN) \u0000are known to exhibit suitable pharmacokinetic properties and good \u0000biocompatibility. The present investigation was designed to evaluate the \u0000effects of NI-SLN on glucose homeostasis, lipid metabolism and liver function \u0000in fructose-induced diabetic rats. NI-SLN was prepared by high pressure \u0000homogenization technique followed by lyophilization with trehalose as \u0000cryoprotectant. Diabetes was induced into rats by the administration of \u0000fructose (10%) in drinking water for six weeks. After induction of diabetes, \u0000rats were divided into four groups for the oral ingestion of NI, NI-SLN and/or \u0000vehicles and their effects on blood glucose levels, oral glucose tolerance test \u0000(OGTT), lipid profile, biochemical parameters, electrolytes and histopathology \u0000were observed. Single dose administration and treatment with NI-SLN showed \u0000significant glucose lowering efficacy in fructose-induced diabetic rats. \u0000Although NI and NI-SLN did not alter the fasting blood glucose level in normal \u0000rats, diabetic rats treated with NI-SLN resulted in significant reduction in \u0000glucose level for 24 hr. In OGTT, NI-SLN exhibited significant \u0000antihyperglycemic activity in both normal and diabetic rats. So, NI-SLN has \u0000better glucose lowering efficacy than that of pure NI in diabetic rats. The \u0000survival rates in rats among the treatment groups were 100%. Treatment with \u0000NI-SLN significantly improved lipid profiles than NI alone and the effect was \u0000dose-dependent. Administration of NI-SLN significantly reduced uric acid, \u0000creatinine levels and maintained a good cationic balance. After two weeks of \u0000NI-SLN treatment, hepatocytes regained their \u0000normal architecture, and the beneficial effect could be correlated with the reduction of SGOT and total bilirubin levels. \u0000Therefore, NI-SLN was found to be \u0000useful for the enhancement of bioavailability and exhibited profound \u0000antidiabetic activity in rats. The results of the study suggested that \u0000NI-SLN exerted better improvement in glucose levels, lipid profiles and organ \u0000protection than pure NI and might have some beneficial effects in the \u0000management of diabetic patients.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80688858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Md. Shah Alam Sarker, R. Barman, Md. Ashraf Ali, Shuji Noguchi, Y. Iwao, S. Itai, M. I. I. Wahed
Atorvastatin calcium (ATV) is a selective competitive inhibitor of HMG CoA reductase characterized by poor aqueous solubility leading to inadequate bioavailability. The present study was designed to develop solid dispersion of atorvastatin (SDA) to improve the solubility and dissolution properties of ATV and evaluation of its in-vivo efficiency in streptozotocin (STZ) induced diabetic mice. Formulations of SDA were prepared by solvent evaporation method using PEG-4000 alone and/or mixture of PEG-4000 and Carplex-80 as carrier in different ratios. Solid-state analyses of SDA were performed to characterize the physicochemical properties of newly developed SDA by differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD), fourier transformed infrared spectra (FTIR) and scanning electron microscopy (SEM). DSC and PXRD showed that the crystallinity of drugs was notably decreased during the preparation of SDA. FTIR and SEM also demonstrated the conversion of ATV from amorphous to crystalline state resulting in improved solubility. Among formulations, SDA-5 showed significant enhancement of in-vitro drug release (around 2 fold higher) as compared to pure ATV. Further, in-vivo study was conducted to evaluate the effects of a newly developed ATV loaded solid dispersion on glycemic control, lipid profile, liver enzyme and histopathology in STZ induced diabetic mice. Oral administration of SDA significantly lowered the blood glucose levels during the course of treatment. Treatment with SDA significantly improved lipid profiles better than ATV alone and the effect was dose-dependent. After one week of SDA treatment significantly decreased liver weights as result of lipid clearance and the hepatocytes regained their normal architecture, and these beneficial effects can be correlated with the reduction of SGPT levels. The results demonstrated that, SDA exerted better glycemic control, lipid lowering effect and organ protection (liver and pancreas) than that of conventional ATV in STZ induced diabetic mice. The mechanism by which SDA conferred better improvement in diabetic conditions can be partially explained by enhancement of solubility and dissolution rate when ATV is loaded in solid dispersion.
{"title":"Formulation Development and In-Vivo Evaluation of Atorvastatin Calcium Solid Dispersion in Streptozotocin Induced Diabetic Mice","authors":"Md. Shah Alam Sarker, R. Barman, Md. Ashraf Ali, Shuji Noguchi, Y. Iwao, S. Itai, M. I. I. Wahed","doi":"10.4236/PP.2018.99030","DOIUrl":"https://doi.org/10.4236/PP.2018.99030","url":null,"abstract":"Atorvastatin calcium (ATV) is a selective competitive inhibitor of HMG CoA reductase characterized by poor aqueous solubility leading to inadequate bioavailability. The present study was designed to develop solid dispersion of atorvastatin (SDA) to improve the solubility and dissolution properties of ATV and evaluation of its in-vivo efficiency in streptozotocin (STZ) induced diabetic mice. Formulations of SDA were prepared by solvent evaporation method using PEG-4000 alone and/or mixture of PEG-4000 and Carplex-80 as carrier in different ratios. Solid-state analyses of SDA were performed to characterize the physicochemical properties of newly developed SDA by differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD), fourier transformed infrared spectra (FTIR) and scanning electron microscopy (SEM). DSC and PXRD showed that the crystallinity of drugs was notably decreased during the preparation of SDA. FTIR and SEM also demonstrated the conversion of ATV from amorphous to crystalline state resulting in improved solubility. Among formulations, SDA-5 showed significant enhancement of in-vitro drug release (around 2 fold higher) as compared to pure ATV. Further, in-vivo study was conducted to evaluate the effects of a newly developed ATV loaded solid dispersion on glycemic control, lipid profile, liver enzyme and histopathology in STZ induced diabetic mice. Oral administration of SDA significantly lowered the blood glucose levels during the course of treatment. Treatment with SDA significantly improved lipid profiles better than ATV alone and the effect was dose-dependent. After one week of SDA treatment significantly decreased liver weights as result of lipid clearance and the hepatocytes regained their normal architecture, and these beneficial effects can be correlated with the reduction of SGPT levels. The results demonstrated that, SDA exerted better glycemic control, lipid lowering effect and organ protection (liver and pancreas) than that of conventional ATV in STZ induced diabetic mice. The mechanism by which SDA conferred better improvement in diabetic conditions can be partially explained by enhancement of solubility and dissolution rate when ATV is loaded in solid dispersion.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79238206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: To analyse antibiotic prescriptions in a cohort of extremely low birth weight neonates admitted to Italian level III Neonatal intensive Care Units. Methods: An online questionnaire was used to collect detailed information for each newborn. Antibiotic prescriptions were classified about their license status and compared with British National Formulary for Children (BNFC) and with a practical guide prepared by the Italian Society of Neonatology (ISN). Results: During the study period (May-July 2014) among 93 neonates admitted to 30 Italian Neonatal intensive Care Units, 56 (60%) received at least an antibiotic (92 prescriptions in total). Ampicillin, gentamicin and vancomycin were the antibiotics most commonly used for the prevention/treatment of bacterial infections. 56/92 antibiotic prescriptions (61%) resulted off-label mainly as regards dosing frequency, while 13 prescriptions (14%) regarded antibiotics used in absence of specific indication for newborns (meropenem, imipenem, piperacillin/tazobactam, clindamycin, clarithromycin). 50/56 neonates (89.3%) received at least one off-label antibiotic prescription. Differences have been observed in dosing regimens between current study and recommendations contained in BNFC, while prescriptions adhered more frequently to ISN indications. Conclusions: Our results confirm the high prevalence of off-label antibiotic use in ELBW neonates and underline a better adherence to indications based on clinical practice.
{"title":"Antibiotic Use in a Cohort of Extremely Low Birth Weight Neonates: Focus on Off-Label Uses and Prescription Behaviour","authors":"L. Cuzzolin, R. Agostino","doi":"10.4236/PP.2018.99029","DOIUrl":"https://doi.org/10.4236/PP.2018.99029","url":null,"abstract":"Aim: To analyse antibiotic prescriptions in a cohort of extremely low birth weight neonates admitted to Italian level III Neonatal intensive Care Units. Methods: An online questionnaire was used to collect detailed information for each newborn. Antibiotic prescriptions were classified about their license status and compared with British National Formulary for Children (BNFC) and with a practical guide prepared by the Italian Society of Neonatology (ISN). Results: During the study period (May-July 2014) among 93 neonates admitted to 30 Italian Neonatal intensive Care Units, 56 (60%) received at least an antibiotic (92 prescriptions in total). Ampicillin, gentamicin and vancomycin were the antibiotics most commonly used for the prevention/treatment of bacterial infections. 56/92 antibiotic prescriptions (61%) resulted off-label mainly as regards dosing frequency, while 13 prescriptions (14%) regarded antibiotics used in absence of specific indication for newborns (meropenem, imipenem, piperacillin/tazobactam, clindamycin, clarithromycin). 50/56 neonates (89.3%) received at least one off-label antibiotic prescription. Differences have been observed in dosing regimens between current study and recommendations contained in BNFC, while prescriptions adhered more frequently to ISN indications. Conclusions: Our results confirm the high prevalence of off-label antibiotic use in ELBW neonates and underline a better adherence to indications based on clinical practice.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77860825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Two selective phosphodiesterase-4 (PDE4) inhibitors—viz., crisaborole (Eucrisa®, Pfizer) and apremilast (Otezla®, Celgene)—have recently received approval by the United States Food and Drug Administration for the treatment of related but different dermatologic skin conditions (viz., atopic dermatitis and plaque psoriasis, respectively). The purpose of this review is to summarize the underlying biochemistry and pathophysiology associated with these dermatologic conditions, review the chemistry, pharmacology and safety of each of these products, and present preclinical and clinical evidence that may help explain why these two PDE4 inhibitors offer new treatment options for these skin conditions.
{"title":"Crisaborole and Apremilast: PDE4 Inhibitors with Similar Mechanism of Action, Different Indications for Management of Inflammatory Skin Conditions","authors":"J. Kitzen, J. Pergolizzi, Robert Taylor, R. Raffa","doi":"10.4236/PP.2018.99028","DOIUrl":"https://doi.org/10.4236/PP.2018.99028","url":null,"abstract":"Two \u0000selective phosphodiesterase-4 (PDE4) inhibitors—viz., crisaborole (Eucrisa®, \u0000Pfizer) and apremilast (Otezla®, Celgene)—have recently received approval by the United \u0000States Food and Drug Administration for the treatment of related but different \u0000dermatologic skin conditions (viz., atopic dermatitis and plaque psoriasis, \u0000respectively). The purpose of this review is to summarize the underlying \u0000biochemistry and pathophysiology associated with these dermatologic conditions, \u0000review the chemistry, pharmacology and safety of each of these products, and \u0000present preclinical and clinical evidence that may help explain why these two \u0000PDE4 inhibitors offer new treatment options for these skin conditions.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89350710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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