Pub Date : 2016-08-09DOI: 10.4172/2167-065X.1000158
K. Fujita, T. Niioka, S. Motoyama, M. Miura
Background: The individual and collective contributions of genetic polymorphisms in drug transporter genes in human renal proximal tubules to cisplatin-induced nephrotoxicity are still unclear. Methods: In this study, we investigated the effects of polymorphisms in SLC22A2 (808G>T), SLC31A1 (rs10981694A>C, rs12686377G>T, rs7851395A>G), SLC47A1 (rs2289669G>A), ABCB1 (1236C>A, 2677G>T/A, 3435C>T), ABCC2 (-24C>T), and ABCG2 (421C>A) on cisplatin-induced nephrotoxicity in 131 patients with esophageal cancer receiving 5-fluorouracil and cisplatin (FP) chemotherapy. The change rate of the estimated glomerular filtration rate (eGFR) was calculated according to the following formula: eGFR before FP chemotherapy-lowest eGFR during first cycle after FP chemotherapy)/eGFR before FP chemotherapy. Results: In univariate analysis, there was a significant correlation between patient age and the change rate of the eGFR by cisplatin (P = 0.021). However, there were no significant differences in the change rate of the eGFR by cisplatin between SLC22A2, SLC47A1, SLC31A1, ABCB1, ABCC2, and ABCG2 polymorphisms. Multivariate analysis revealed that only age was an independent variable predicting a higher risk of cisplatin-induced acute renal dysfunction. Conclusion: In FP chemotherapy for esophageal cancer patients, cisplatin-induced nephrotoxicity was not affected by polymorphisms in the uptake transporters OCT2 and Ctr1 or efflux transporters MATE1, P-glycoprotein, MRP2, and BCRP. Since degradation of renal function due to aging reduces cisplatin clearance, the cisplatin dosage should be carefully chosen in elderly patients.
{"title":"Influence of Renal ABC and SLC Transporter Polymorphisms on Cisplatin-induced Nephrotoxicity in Patients with Esophageal Cancer","authors":"K. Fujita, T. Niioka, S. Motoyama, M. Miura","doi":"10.4172/2167-065X.1000158","DOIUrl":"https://doi.org/10.4172/2167-065X.1000158","url":null,"abstract":"Background: The individual and collective contributions of genetic polymorphisms in drug transporter genes in human renal proximal tubules to cisplatin-induced nephrotoxicity are still unclear. Methods: In this study, we investigated the effects of polymorphisms in SLC22A2 (808G>T), SLC31A1 (rs10981694A>C, rs12686377G>T, rs7851395A>G), SLC47A1 (rs2289669G>A), ABCB1 (1236C>A, 2677G>T/A, 3435C>T), ABCC2 (-24C>T), and ABCG2 (421C>A) on cisplatin-induced nephrotoxicity in 131 patients with esophageal cancer receiving 5-fluorouracil and cisplatin (FP) chemotherapy. The change rate of the estimated glomerular filtration rate (eGFR) was calculated according to the following formula: eGFR before FP chemotherapy-lowest eGFR during first cycle after FP chemotherapy)/eGFR before FP chemotherapy. Results: In univariate analysis, there was a significant correlation between patient age and the change rate of the eGFR by cisplatin (P = 0.021). However, there were no significant differences in the change rate of the eGFR by cisplatin between SLC22A2, SLC47A1, SLC31A1, ABCB1, ABCC2, and ABCG2 polymorphisms. Multivariate analysis revealed that only age was an independent variable predicting a higher risk of cisplatin-induced acute renal dysfunction. Conclusion: In FP chemotherapy for esophageal cancer patients, cisplatin-induced nephrotoxicity was not affected by polymorphisms in the uptake transporters OCT2 and Ctr1 or efflux transporters MATE1, P-glycoprotein, MRP2, and BCRP. Since degradation of renal function due to aging reduces cisplatin clearance, the cisplatin dosage should be carefully chosen in elderly patients.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83343691","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}
Pub Date : 2016-05-31DOI: 10.4172/2167-065X.1000157
B. Ramu, Ameedi
In Uganda in the year 1947, Zika virus was identified from a febrile sentinel rhesus monkey and from a group of Aedes africanus mosquitoes which are frequently found in Zika forest (in Uganda) which was noted at the time of investigation of yellow fever [1]. In east Africa 1952 Zika virus was firstly detected in humans by using neutralizing antibody testing in sera. Zika virus was initially identified in the population of Uganda people [1-4]. This Zika virus is caused by RNA flavivirus closely related to that of dengue infected to human by Aedes aegyptis and Aedes albopictus mosquitoes. Most of the infections caused by Zika virus are asymptomatic, symptomatic infections are caused by a self limiting febrile illness of 4-7 days accompanied by various symptoms.
{"title":"Recent Outbreak of Zika Virus Threat for Pregnant Women","authors":"B. Ramu, Ameedi","doi":"10.4172/2167-065X.1000157","DOIUrl":"https://doi.org/10.4172/2167-065X.1000157","url":null,"abstract":"In Uganda in the year 1947, Zika virus was identified from a febrile sentinel rhesus monkey and from a group of Aedes africanus mosquitoes which are frequently found in Zika forest (in Uganda) which was noted at the time of investigation of yellow fever [1]. In east Africa 1952 Zika virus was firstly detected in humans by using neutralizing antibody testing in sera. Zika virus was initially identified in the population of Uganda people [1-4]. This Zika virus is caused by RNA flavivirus closely related to that of dengue infected to human by Aedes aegyptis and Aedes albopictus mosquitoes. Most of the infections caused by Zika virus are asymptomatic, symptomatic infections are caused by a self limiting febrile illness of 4-7 days accompanied by various symptoms.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74109959","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}
Pub Date : 2016-05-26DOI: 10.4172/2167-065X.1000E124
S. Shanmugam
Oral films, a promising novel drug delivery system, are a strip of single or multilayered, mucoadhesive or non-mucoadhesive, thin polymeric films that are intended to deliver active therapeutic moieties either locally or systemically in oral cavity through sublingual, buccal, palatal, or gastrointestinal absorption [1-3]. In general, films are known by several names including but not limited to orodispersible films [4], orally disintegrating/dissolving films [5,6], rapid/fast/quick dissolving films [7-10], oral soluble films [11], oral thin films [12], strip films [1,13,14], quick disintegrating/dissolving films [8], buccal or buccal soluble film [15], mucoadhesive films [16], transmucosal films [17], sublingual films [18], etc. Strip films or thin films could be considered as a broad spectrum of classification or superset of films that might include all kinds of film applications for oral, topical/transdermal, vaginal, etc. Consequently, the focus of this topic, oral films, are generally strip or thin films intended for oral application, i.e., either oral cavity or gastrointestinal tract, and can generally be classified into oromucosal films and orodispersible films.
{"title":"Oral Films: A Look Back","authors":"S. Shanmugam","doi":"10.4172/2167-065X.1000E124","DOIUrl":"https://doi.org/10.4172/2167-065X.1000E124","url":null,"abstract":"Oral films, a promising novel drug delivery system, are a strip of single or multilayered, mucoadhesive or non-mucoadhesive, thin polymeric films that are intended to deliver active therapeutic moieties either locally or systemically in oral cavity through sublingual, buccal, palatal, or gastrointestinal absorption [1-3]. In general, films are known by several names including but not limited to orodispersible films [4], orally disintegrating/dissolving films [5,6], rapid/fast/quick dissolving films [7-10], oral soluble films [11], oral thin films [12], strip films [1,13,14], quick disintegrating/dissolving films [8], buccal or buccal soluble film [15], mucoadhesive films [16], transmucosal films [17], sublingual films [18], etc. Strip films or thin films could be considered as a broad spectrum of classification or superset of films that might include all kinds of film applications for oral, topical/transdermal, vaginal, etc. Consequently, the focus of this topic, oral films, are generally strip or thin films intended for oral application, i.e., either oral cavity or gastrointestinal tract, and can generally be classified into oromucosal films and orodispersible films.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89768684","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}
Pub Date : 2016-05-26DOI: 10.4172/2167-065X.1000E123
Hannah M. Jester, A. Al-Achi
Dementia is a condition that currently affects over 46 million people worldwide [1]. It is a growing problem of epidemic proportions and while efforts are being made to treat it, the prevalence is estimated to affect over 131 million by the year 2050 [1]. Alzheimer’s disease (AD) is the most common form of dementia seen today, comprising 60-70% of all diagnosed cases of dementia [2]. The purpose of this editorial is to review the potential benefits of the Mediterranean diet and some botanicals on AD.
{"title":"Does The Mediterranean Diet or Botanicals Influence Alzheimer’s Disease?","authors":"Hannah M. Jester, A. Al-Achi","doi":"10.4172/2167-065X.1000E123","DOIUrl":"https://doi.org/10.4172/2167-065X.1000E123","url":null,"abstract":"Dementia is a condition that currently affects over 46 million people worldwide [1]. It is a growing problem of epidemic proportions and while efforts are being made to treat it, the prevalence is estimated to affect over 131 million by the year 2050 [1]. Alzheimer’s disease (AD) is the most common form of dementia seen today, comprising 60-70% of all diagnosed cases of dementia [2]. The purpose of this editorial is to review the potential benefits of the Mediterranean diet and some botanicals on AD.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75704390","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}
Pub Date : 2016-05-17DOI: 10.4172/2167-065X.1000156
Mervat Mostafa Omran, O. Badary, A. Helal, S. Shouman
Abstract Purpose: To study the correlation between pharmacokinetics & pharmacodynamic of docetaxel and CYP3A4 activity in Egyptian cancer patients. Patients and methods: Fourteen Egyptian female Patients with metastatic breast cancer, World Health Organization (WHO) performance status 0 to 2, had received prior chemotherapy regimen, were treated with single-agent docetaxel (100 mg/m2), given every 21 days. Hydrocortisone 300 mg IV was administered 2 days before docetaxel treatment and Cytochrome 3A4 activity was determined by measuring the level of urinary metabolites of 6β-hydroxy cortisol (6β-OHF) and cortisol (FC). For the pharmacokinetic study, Blood samples were taken before and after IV infusion for 1 hr of 100 mg/m2 docetaxel. The level of the drug was determined using HPLC and the correlation between pharmacokinetics and CYP3A4 activity were determined. Results: After cortisol administration, the total amount of 24-hour urinary 6β-OHF and FC were19.97 ± 10.43 and 16.84 ± 10.36 mg/24 h (mean ± SD) respectively. On the other hand, the 6β-OHF/FC ratio after cortisol administration was 1.86 ± 1.933. The pharmacokinetic parameters of docetaxel were clearance 19.9 ± 4.5 L/hr, the volume of distribution 65.6 ± 28.6 L (mean ± SD) and AUC 7.2 μg/ml.hr (range 5-8.8 μg/ml.hr) ± SD). A significant correlation was found between 6β-OHF/FC ratio and neutropenia (p=0.04) in addition correlation between 6β-OHF and Cmax (p=0.04). Conclusion: The interpatient variability of CYP3A4 activity in each patient could be predicted by measuring the total amount of 24 hour urinary 63-OHF after cortisol administration. Individualized dosing to optimize drug exposure for each patient could be performed based on this method. A farther study of fixed versus individualized dosing of docetaxel is needed to determine whether individualized chemotherapy with the application of this method can reduce PK and toxicity variability.
摘要目的:研究多西他赛药动学和药效学与埃及肿瘤患者CYP3A4活性的相关性。患者和方法:14例埃及女性转移性乳腺癌患者，世界卫生组织(WHO)评分为0 ~ 2，既往接受化疗方案，多西他赛单药治疗(100 mg/m2)，每21天给药一次。在多西他赛治疗前2天给予氢化可的松300 mg IV，通过测定尿中6β-羟基皮质醇(6β-OHF)和皮质醇(FC)的代谢物水平来测定细胞色素3A4的活性。为了进行药代动力学研究，在静脉输注100 mg/m2多西紫杉醇1小时前后取血样。采用高效液相色谱法测定药物水平，并测定药代动力学与CYP3A4活性的相关性。结果:皮质醇给药后，24小时尿6β-OHF和FC总量分别为19.97±10.43和16.84±10.36 mg/24 h (mean±SD)。另一方面，皮质醇处理后6β-OHF/FC比值为1.86±1.933。多西他赛的清除率为19.9±4.5 L/hr，分布容积为65.6±28.6 L (mean±SD)， AUC为7.2 μg/ml。(范围5-8.8 μg/ml.hr)±SD)。6β-OHF/FC与中性粒细胞减少症有显著相关(p=0.04)， 6β-OHF与Cmax有显著相关(p=0.04)。结论:通过测量皮质醇给药后24小时尿63-OHF总量，可以预测患者间CYP3A4活性的变异性。个体化给药以优化每位患者的药物暴露，可基于该方法进行。需要进一步研究多西他赛的固定剂量和个体化剂量，以确定应用该方法进行个体化化疗是否可以降低PK和毒性变异性。
{"title":"A Prospective Pharmacokinetic Study of Docetaxel in Breast Cancer Patients in Relation to CYP3A4 Activity","authors":"Mervat Mostafa Omran, O. Badary, A. Helal, S. Shouman","doi":"10.4172/2167-065X.1000156","DOIUrl":"https://doi.org/10.4172/2167-065X.1000156","url":null,"abstract":"Abstract \u0000Purpose: To study the correlation between pharmacokinetics & pharmacodynamic of docetaxel and CYP3A4 activity in Egyptian cancer patients. \u0000Patients and methods: Fourteen Egyptian female Patients with metastatic breast cancer, World Health Organization (WHO) performance status 0 to 2, had received prior chemotherapy regimen, were treated with single-agent docetaxel (100 mg/m2), given every 21 days. Hydrocortisone 300 mg IV was administered 2 days before docetaxel treatment and Cytochrome 3A4 activity was determined by measuring the level of urinary metabolites of 6β-hydroxy cortisol (6β-OHF) and cortisol (FC). For the pharmacokinetic study, Blood samples were taken before and after IV infusion for 1 hr of 100 mg/m2 docetaxel. The level of the drug was determined using HPLC and the correlation between pharmacokinetics and CYP3A4 activity were determined. \u0000Results: After cortisol administration, the total amount of 24-hour urinary 6β-OHF and FC were19.97 ± 10.43 and 16.84 ± 10.36 mg/24 h (mean ± SD) respectively. On the other hand, the 6β-OHF/FC ratio after cortisol administration was 1.86 ± 1.933. The pharmacokinetic parameters of docetaxel were clearance 19.9 ± 4.5 L/hr, the volume of distribution 65.6 ± 28.6 L (mean ± SD) and AUC 7.2 μg/ml.hr (range 5-8.8 μg/ml.hr) ± SD). A significant correlation was found between 6β-OHF/FC ratio and neutropenia (p=0.04) in addition correlation between 6β-OHF and Cmax (p=0.04). \u0000Conclusion: The interpatient variability of CYP3A4 activity in each patient could be predicted by measuring the total amount of 24 hour urinary 63-OHF after cortisol administration. Individualized dosing to optimize drug exposure for each patient could be performed based on this method. A farther study of fixed versus individualized dosing of docetaxel is needed to determine whether individualized chemotherapy with the application of this method can reduce PK and toxicity variability.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84332468","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}
Pub Date : 2016-04-12DOI: 10.4172/2167-065X.1000155
R. Agabio, Anna Maria Giulia Farci, Olga Curreli, Raffaele Deidda, S. Mercuro, Romina Naitana, A. Restivo, E. Tronci, G. Gessa, M. R. Melis
Background Preclinical studies suggest that the neuropeptide oxytocin reduces food intake and body weight, but only a few clinical studies have investigated the translatability of these findings in humans. The present study investigated the safety and efficacy of oxytocin nasal spray in patients affected by binge eating disorder and obesity. Methods Seventeen outpatients affected by binge eating disorder and obesity participated in a 8 week double-blind trial and received oxytocin (n=8; 24 IU, four times a day, 20 min before each of three meals and before going to bed) or placebo (n=9) with an energy-restricted diet. Primary outcomes included adverse events and the number of binge eating episodes per week. Secondary measures included body weight, BMI, severity of BED, craving for food, quality of sleep, quality of life, anxiety, and depressive symptoms. Results One patient of oxytocin group discontinued prematurely the trial before the first post-randomization efficacy measure. Among the other 16 participants, 13 (81.2%) completed the trial, and 3 (18.8%) discontinued [3 in the oxytocin group; 0 in the placebo group (p=0.0625, Fisher’s exact test)]. No significant difference between groups was found in any outcome evaluated. Patients of the placebo group performed slightly better than patients of the oxytocin group in some secondary outcomes, but these differences were not significant. Conclusion Oxytocin nasal spray resulted to be safe, including in women of childbearing age but did not significantly reduce the number of binge eating episodes per week in outpatients affected by binge eating disorder and obesity. These findings are discussed in light of the human oxytocin literature.
{"title":"Oxytocin Nasal Spray in the Treatment of Binge Eating Disorder and Obesity: A Pilot, Randomized, Double-Blind Trial","authors":"R. Agabio, Anna Maria Giulia Farci, Olga Curreli, Raffaele Deidda, S. Mercuro, Romina Naitana, A. Restivo, E. Tronci, G. Gessa, M. R. Melis","doi":"10.4172/2167-065X.1000155","DOIUrl":"https://doi.org/10.4172/2167-065X.1000155","url":null,"abstract":"Background \u0000Preclinical studies suggest that the neuropeptide oxytocin reduces food intake and body weight, but only a few clinical studies have investigated the translatability of these findings in humans. The present study investigated the safety and efficacy of oxytocin nasal spray in patients affected by binge eating disorder and obesity. \u0000Methods \u0000Seventeen outpatients affected by binge eating disorder and obesity participated in a 8 week double-blind trial and received oxytocin (n=8; 24 IU, four times a day, 20 min before each of three meals and before going to bed) or placebo (n=9) with an energy-restricted diet. Primary outcomes included adverse events and the number of binge eating episodes per week. Secondary measures included body weight, BMI, severity of BED, craving for food, quality of sleep, quality of life, anxiety, and depressive symptoms. \u0000Results \u0000One patient of oxytocin group discontinued prematurely the trial before the first post-randomization efficacy measure. Among the other 16 participants, 13 (81.2%) completed the trial, and 3 (18.8%) discontinued [3 in the oxytocin group; 0 in the placebo group (p=0.0625, Fisher’s exact test)]. No significant difference between groups was found in any outcome evaluated. Patients of the placebo group performed slightly better than patients of the oxytocin group in some secondary outcomes, but these differences were not significant. \u0000Conclusion \u0000Oxytocin nasal spray resulted to be safe, including in women of childbearing age but did not significantly reduce the number of binge eating episodes per week in outpatients affected by binge eating disorder and obesity. These findings are discussed in light of the human oxytocin literature.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90087880","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}
Pub Date : 2016-03-24DOI: 10.4172/2167-065X.1000154
K. Naruhashi, Akiko Kamino, E. Ochi, Erina Kusabiraki, M. Ueda, Yuusuke Sugihara, T. Urushidani, Hirokazu Nakanishi, N. Shibata
Abstract 1.1. Introduction: The μ opioid receptor agonists, morphine and loperamide, are widely used orally and are suggested to be P-glycoprotein (P-gp) substrates. P-gp is expressed in the brain, intestine, and various tissues in human and rats. In the intestine, P-gp limits the absorption of certain drugs such as opioids; however, the underlying mechanism has not been elucidated. The aim of the present study was to examine the intestinal transport characteristics of morphine and loperamide and the role of P-gp in their transport process. 1.2. Method: Transcellular transport studies were conducted using isolated rat intestinal tissue mounted in an Ussing-type chamber. Bidirectional permeability and inhibition transport studies were performed using Caco-2 cell lines. The intestinal absorption was examined by an in situ closed-loop method in rats. 1.3. Results: Loperamide showed secretory transport across rat intestinal tissue and Caco-2 cells, and P-gp substrates cyclosporine A and rhodamine 123 inhibited this transport. In the intestinal loop experiment in rats, the accumulation of loperamide in the intestinal tissue increased upon adding cyclosporine A and rhodamine 123. In contrast, morphine showed no directional transport and P-gp inhibitory effects across rat intestinal tissue. In Caco-2 cells, morphine transport was found to be secretory-directed and this transport was inhibited by cyclosporine A and rhodamine 123, but to a much lesser extent than that of loperamide. Morphine disappearance and accumulation were unaffected upon the addition of cyclosporine A and rhodamine 123. 1.4. Conclusion: These results suggest that P-gp contributes significantly to the secretory transport of loperamide but negligibly to that of morphine in the small intestine. In conclusion, intestinal transport of both morphine and loperamide is found to be secretory-directed. P-gp partially contributes to this secretory-directed transport. Thus, P-gp is prominent in loperamide rather than morphine transport.
{"title":"Transport Mechanism of Intestinal Absorption of ü Opioid Recept or Agonists and Contribution of P-Glycoprotein in Rats and Human Intestinal Epithelial Caco-2","authors":"K. Naruhashi, Akiko Kamino, E. Ochi, Erina Kusabiraki, M. Ueda, Yuusuke Sugihara, T. Urushidani, Hirokazu Nakanishi, N. Shibata","doi":"10.4172/2167-065X.1000154","DOIUrl":"https://doi.org/10.4172/2167-065X.1000154","url":null,"abstract":"Abstract \u00001.1. Introduction: The μ opioid receptor agonists, morphine and loperamide, are widely used orally and are suggested to be P-glycoprotein (P-gp) substrates. P-gp is expressed in the brain, intestine, and various tissues in human and rats. In the intestine, P-gp limits the absorption of certain drugs such as opioids; however, the underlying mechanism has not been elucidated. The aim of the present study was to examine the intestinal transport characteristics of morphine and loperamide and the role of P-gp in their transport process. \u00001.2. Method: Transcellular transport studies were conducted using isolated rat intestinal tissue mounted in an Ussing-type chamber. Bidirectional permeability and inhibition transport studies were performed using Caco-2 cell lines. The intestinal absorption was examined by an in situ closed-loop method in rats. \u00001.3. Results: Loperamide showed secretory transport across rat intestinal tissue and Caco-2 cells, and P-gp substrates cyclosporine A and rhodamine 123 inhibited this transport. In the intestinal loop experiment in rats, the accumulation of loperamide in the intestinal tissue increased upon adding cyclosporine A and rhodamine 123. In contrast, morphine showed no directional transport and P-gp inhibitory effects across rat intestinal tissue. In Caco-2 cells, morphine transport was found to be secretory-directed and this transport was inhibited by cyclosporine A and rhodamine 123, but to a much lesser extent than that of loperamide. Morphine disappearance and accumulation were unaffected upon the addition of cyclosporine A and rhodamine 123. \u00001.4. Conclusion: These results suggest that P-gp contributes significantly to the secretory transport of loperamide but negligibly to that of morphine in the small intestine. In conclusion, intestinal transport of both morphine and loperamide is found to be secretory-directed. P-gp partially contributes to this secretory-directed transport. Thus, P-gp is prominent in loperamide rather than morphine transport.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76675878","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}
Pub Date : 2015-12-24DOI: 10.4172/2167-065X.C1.015
R. Santos
ISSN: 2573-3664 Coffee is among the most widely consumed beverages in the world. The consumption of coffee has been receiving a lot of attention in regards its potential health benefits and risks as well. Caffeine and phenolic compounds such as chlorogenic acids are some of the most investigated constituents from coffee. It has been attributed various properties to those compounds such as central nervous system stimulant and antioxidants respectively. Coffee is in fact a very complex mixture that varies according with the origin of the beans and roasting process.
{"title":"Coffee consumption: A genetic approach","authors":"R. Santos","doi":"10.4172/2167-065X.C1.015","DOIUrl":"https://doi.org/10.4172/2167-065X.C1.015","url":null,"abstract":"ISSN: 2573-3664 Coffee is among the most widely consumed beverages in the world. The consumption of coffee has been receiving a lot of attention in regards its potential health benefits and risks as well. Caffeine and phenolic compounds such as chlorogenic acids are some of the most investigated constituents from coffee. It has been attributed various properties to those compounds such as central nervous system stimulant and antioxidants respectively. Coffee is in fact a very complex mixture that varies according with the origin of the beans and roasting process.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75992065","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}
Pub Date : 2015-12-24DOI: 10.4172/2167-065X.C1.016
F. Al-Saikhan
N antimicrobial stewardship is continuous work to optimize antimicrobial usage to improve patient outcomes and prevent antimicrobial related problems. General Administration of Pharmaceutical Care established the program in 2013 by formulate Central Antibiotic Committees, this committee established National Antimicrobial Stewardship program consisting of formulating peripheral antibiotics, infectious diseases team, antibiotics physician order form, antibiotics consumption and usages, antibiogram regulations, and USA General of Disease Control Antimicrobial stewardship monitoring outcome indicators. In 2014, Peripheral Antibiotics Committees were established at twenty regions to follow up the implementation of the program national wide, and started with antimicrobial stewardship education and orientation. In 2015, the real applications of the program were started in more than ten regions and more than forty hospitals. Antimicrobial stewardship will be expanded to cover 20 regions and more ninety biggest hospitals, medical cities and private hospitals and primary care centers in Saudi Arabia. The program is excepting to reduce antimicrobial consumption more than 50% with reduction of bugs resistance to medication, reduction of antimicrobial related problems, better patients care with tremendous reduction of unnecessary cost.
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