F. Ibarra-Velarde, Y. Vera‐Montenegro, Yazmín Acala-Canto, I. Cruz-Mendoza
The acaricidal efficiency of fipronil alone and fipronil + methoprene compared to commercial fipronil and commercial fipronil + methoprene, applied by the epicutaneous route (spot-on) in dogs naturally infested with ticks, was assessed. Thirty dogs infested with high loads of ticks were used. On day 0, the dogs were divided into 5 groups of 6 animals each. Each animal was duly identified for individual and group monitoring. Treatments were made based on body weight according to manufacturer’s instructions. Group 1 (G1) received 10.0% fipronil at a single dose of a pipette applied by epicutaneous route in the base of the neck. G2 received 10% fipronil + 10% methoprene in single application similarly to G1. G3 was treated with 9.8% commercial fipronil as before mentioned. G4 received commercial 9.8% fipronil + 9.8% methoprene applied as in previous groups. G5 served as an infected untreated control. Animals were examined by thumb tick counts on days 0 (Treatment day), 3, 7, 14, 21 and 28. Efficacy was measured as a percentage of tick reduction in the treated groups relative to the untreated control. Results indicated an overall efficacy of 88.2%, 93%, 90.4% and 99.3%, respectively. There was no significant statistical difference between the treated groups (P ly and in full development. It is concluded that the combined formulations of fipronil + methoprene compared to fipronil applied alone, showed an additive effect against Rhipicephalus sanguineus ticks in naturally infested dogs kept in captivity.
{"title":"Additive Efficiency of Fipronil + Methoprene Compared to Fipronil Alone against Rhipicephalus sanguineus Ticks in Naturally Infested Dogs","authors":"F. Ibarra-Velarde, Y. Vera‐Montenegro, Yazmín Acala-Canto, I. Cruz-Mendoza","doi":"10.4236/pp.2020.118016","DOIUrl":"https://doi.org/10.4236/pp.2020.118016","url":null,"abstract":"The acaricidal efficiency of fipronil alone and fipronil \u0000+ methoprene compared to commercial fipronil and commercial fipronil + methoprene, \u0000applied by the epicutaneous route (spot-on) in dogs naturally infested with \u0000ticks, was assessed. Thirty dogs infested with high loads of ticks were used. \u0000On day 0, the dogs were divided into 5 groups of 6 animals each. Each animal \u0000was duly identified for individual and group monitoring. Treatments were made \u0000based on body weight according to manufacturer’s instructions. Group 1 (G1) received 10.0% fipronil \u0000at a single dose of a pipette applied by epicutaneous route in the base of the neck. G2 received 10% fipronil \u0000+ 10% methoprene in single application similarly to G1. G3 was treated with \u00009.8% commercial fipronil as before mentioned. G4 received commercial 9.8% fipronil \u0000+ 9.8% methoprene applied as in previous groups. G5 served as an infected \u0000untreated control. Animals were examined by thumb \u0000tick counts on days 0 (Treatment day), 3, 7, 14, 21 and 28. Efficacy was \u0000measured as a percentage of tick reduction in the treated groups relative to \u0000the untreated control. Results indicated an overall efficacy of 88.2%, 93%, \u000090.4% and 99.3%, respectively. There was no significant statistical difference \u0000between the treated groups (P ly and in full development. It is concluded that the combined formulations \u0000of fipronil + methoprene compared to fipronil applied alone, showed an additive \u0000effect against Rhipicephalus sanguineus ticks \u0000in naturally infested dogs kept in captivity.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87928690","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 stem bark of Baccaurea ramiflora was studied. Four aldehydes named as 3 methoxy 4 hydroxy-cinnamaldehyde (coniferyl aldehyde); 3, 4, 5 trimethoxy cinnamaldehyde; 3, 4, 5 trimethoxy benzaldehyde and 3,4 dimethoxy benzaldehyde) (veratraldehyde) have been isolated and then identified by NMR spectroscopy. All of them are first time reported for this plant. Here in vitro biological investigations include antioxidant and cytotoxicity study. Among all fractions, the chloroform soluble fraction exhibited strong free radical scavenging activity having IC50 value of 12.87 μg/ml compared to BHT (IC50 value 5.64 μg/ml). On the contrary, aqueous soluble fraction exhibited most toxicity towards brine shrimp compared with vincristine sulphate having LC50 value of 1.44 and 0.9258 μg/ml respectively.
{"title":"Baccaurea ramiflora: Isolation of Aldehydes and in Vitro Biological Investigations","authors":"Sangita Debnath Puja, C. Hasan, M. Ahsan","doi":"10.4236/pp.2020.117014","DOIUrl":"https://doi.org/10.4236/pp.2020.117014","url":null,"abstract":"The stem bark of Baccaurea \u0000ramiflora was studied. Four aldehydes named as 3 methoxy 4 hydroxy-cinnamaldehyde (coniferyl \u0000aldehyde); 3, 4, 5 trimethoxy cinnamaldehyde; 3, 4, 5 trimethoxy benzaldehyde and 3,4 dimethoxy benzaldehyde) \u0000(veratraldehyde) have been isolated and then identified by NMR spectroscopy. \u0000All of them are first time reported for this plant. Here in vitro biological investigations include antioxidant and \u0000cytotoxicity study. Among all fractions, the chloroform soluble fraction exhibited \u0000strong free radical scavenging activity having IC50 value of 12.87 μg/ml \u0000compared to BHT (IC50 value 5.64 μg/ml). On the contrary, aqueous \u0000soluble fraction exhibited most toxicity towards brine shrimp compared with \u0000vincristine sulphate having LC50 value of 1.44 and 0.9258 μg/ml respectively.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86540700","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}
There are many natural sources to obtain pharmaceutical grade starch, one of which is banana (Musa × paradisiaca L.); nevertheless, the use of native starch has certain disadvantages compared to modified starches, whose disintegrating properties are better. In this study, starch extracted from rejected fruits of Musa × paradisiaca L., was modified by acetylation, under the following optimized experimental conditions: 130 mL acetic anhydride, 3 mL sodium hydroxide 50% p/v for each 15 grams of native starch, at 123℃ during 3 hours. The reaction resulted in a modified green banana starch with twice as much swelling capacity compared to unmodified (native) starch; acetylation was verified by infrared spectroscopy and degree of substitution of acetyl groups by back titration. The dissolution profiles of Ibuprofen tablets made with banana modified starch and commercial disintegrant, have no differences according with their similarity factor, f2. It is concluded that it is feasible to use green banana starch modified through acetylation as a pharmaceutical disintegrant.
{"title":"Acetylation of Starch Extracted from Rejected Fruits of Musa × paradisiaca L. to Obtain a Pharmaceutical Disintegrant","authors":"Karla Dumancela, E. Mayorga, J. Aguirre","doi":"10.4236/pp.2020.116011","DOIUrl":"https://doi.org/10.4236/pp.2020.116011","url":null,"abstract":"There are many natural sources to obtain \u0000pharmaceutical grade starch, one of which is banana (Musa × paradisiaca L.); nevertheless, the use of native starch \u0000has certain disadvantages compared to modified starches, whose disintegrating \u0000properties are better. In this study, starch extracted from rejected fruits of Musa × paradisiaca L., was modified by acetylation, under the \u0000following optimized experimental conditions: 130 mL acetic anhydride, 3 mL \u0000sodium hydroxide 50% p/v for each 15 grams of native starch, at 123℃ during 3 \u0000hours. The reaction resulted in a modified green banana starch with twice as \u0000much swelling capacity compared to unmodified (native) starch; acetylation was \u0000verified by infrared spectroscopy and degree of substitution of acetyl groups by \u0000back titration. The dissolution profiles of Ibuprofen tablets made with banana modified starch and commercial disintegrant, \u0000have no differences according with their similarity factor, f2. It is concluded that it is feasible to use green \u0000banana starch modified through acetylation as a pharmaceutical disintegrant.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81820419","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}
Invasive candidiasis was the most common nosocomial fungal infection with high morbidity and mortality, which is mainly occurring in immunodeficiency and critical patients. Echinocandins were recommended as first-line drugs for the treatment and prevention of invasive candidiasis. In our study, we aimed to optimize the dosage of Rezafungin against Candida spp. based on pharmacokinetic/pharmacodynamics (PK/PD) analysis. We collected the published data about pharmacokinetic parameters of rezafungin and the MIC distribution of Candida spp. on rezafungin. Monte Carlo simulation was used to calculate probability of target attainment and a cumulative fraction of response to assess the best dosing regimen. The optimal dosage regimen for C. albicans and C. glabrata was 50 mg IV, and the optimal dosage regimen for C. parapsilosis was 100 mg IV. Lastly, rezafungin has an excellent antifungal effect on C. albicans, C. glabrata and C. parapsilosis.
{"title":"Optimization of Dosage Regimen of Rezafungin against Candida spp. Based on Pharmacokinetic/Pharmacodynamic Analysis","authors":"Jiuli Hu, Junhui Hu","doi":"10.4236/pp.2020.116008","DOIUrl":"https://doi.org/10.4236/pp.2020.116008","url":null,"abstract":"Invasive candidiasis was the most common nosocomial fungal infection with \u0000high morbidity and mortality, which is mainly occurring in immunodeficiency and \u0000critical patients. Echinocandins were recommended as first-line drugs for the \u0000treatment and prevention of invasive candidiasis. In our study, we aimed to optimize \u0000the dosage of Rezafungin against Candida spp. based on \u0000pharmacokinetic/pharmacodynamics (PK/PD) analysis. We collected the published \u0000data about pharmacokinetic parameters of rezafungin and the MIC distribution of Candida spp. on rezafungin. Monte Carlo simulation was used to calculate \u0000probability of target attainment and a cumulative fraction of response to \u0000assess the best dosing regimen. The optimal dosage regimen for C. albicans and C. glabrata was 50 mg \u0000IV, and the optimal dosage regimen for C. parapsilosis was \u0000100 mg IV. Lastly, rezafungin has an excellent antifungal effect on C. albicans, C. glabrata and C. parapsilosis.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85778763","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}
There is extensive worldwide use for the social consumption of alcohol. Abuse of alcohol causes substantial personal, psychological and medical health issues. In addition, there are significant national economic costs from lost productivity. However, there are limited pharmaceutical drugs for the treatment of alcohol overuse. Historically, many cultures have used herbs and other natural compounds to reduce problematic alcohol induced behaviour but the evidence is anecdotal. This study investigated if a natural compound formula (RM88) that was developed could reduce blood alcohol concentration (BAC) in a controlled case series. Thirteen subjects (5 males, 8 females, age range 18 to 85 years) completed 16 paired sessions of alcohol only versus RM88 with alcohol. Subjects consumed one to three standard drinks of beer, wine or spirits (14.7 to 29.4 gm alcohol). Measurements were made by a fuel cell breathalyzer for a period of 90 minutes. Summated BAC showed a reduction in 94% (15/16) of paired test sessions (BAC reduction range 23% - 79%, mean 50.9% ± 16.5%, p = 0.0005). Data normalized to 20 gm alcohol (two standard drinks) showed a significance of p = 0.00026. One subject on prednisone and hydroxychloroquine drugs had increased BAC from RM88. The average reductions of BAC for the beverages were spirits 34% (n = 3), beer 36% (n = 3), and wine 52% (n = 10). RM88 showed that this combination of natural compounds was very effective in reducing maximal peak concentrations of alcohol.
{"title":"Natural Compound Formula RM88 Significantly Reduces Blood Alcohol Concentration in Humans","authors":"E. R. Vickers","doi":"10.4236/pp.2020.116010","DOIUrl":"https://doi.org/10.4236/pp.2020.116010","url":null,"abstract":"There is extensive worldwide \u0000use for the social consumption of alcohol. Abuse of alcohol causes substantial \u0000personal, psychological and medical health issues. In addition, there are \u0000significant national economic costs from lost productivity. However, there are \u0000limited pharmaceutical drugs for the treatment of alcohol overuse. Historically, \u0000many cultures have used herbs and other natural compounds to reduce problematic \u0000alcohol induced behaviour but the evidence is anecdotal. This study \u0000investigated if a natural compound formula (RM88) that was developed could \u0000reduce blood alcohol concentration (BAC) in a controlled case series. Thirteen \u0000subjects (5 males, 8 females, age range 18 to 85 years) completed 16 paired \u0000sessions of alcohol only versus RM88 with alcohol. Subjects consumed one to \u0000three standard drinks of beer, wine or spirits (14.7 to 29.4 gm alcohol). \u0000Measurements were made by a fuel cell breathalyzer for a period of 90 minutes. \u0000Summated BAC showed a reduction in 94% (15/16) of paired test sessions (BAC \u0000reduction range 23% - 79%, mean 50.9% ± 16.5%, p = 0.0005). Data normalized to \u000020 gm alcohol (two standard drinks) showed a significance of p = 0.00026. One \u0000subject on prednisone and hydroxychloroquine drugs had increased BAC from RM88. \u0000The average reductions of BAC for the beverages were spirits 34% (n = 3), beer 36% (n = 3), and wine 52% \u0000(n = 10). RM88 showed that this combination of natural compounds was very \u0000effective in reducing maximal peak concentrations of alcohol.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81785259","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 objective of this study was to investigate the probability of target attainment of various posaconazole dosing regimens against Mucorales species in patients with mucormycosis. According to pharmacokinetic/pharmacodynamic parameters of posaconazole in adults, the dosage regimen of posaconazole for mucormycosis included 50, 100, 200 and 400 mg orally q12h. Monte Carlo Simulation analysed the published parameters of pharmacokinetics and the MIC values of mucormycosis in Mucorales species. The results showed that posaconazole did not affect Rhizopus arrhizus and Mucor sp. The optimal dosage of posaconazole for Rhizopus microsporus and Rhizomucor pusillus was 400 mg orally q12h and the best dosage regimen for Lichtheimia corymbifera was 200 mg orally q12h. The antifungal activity of posaconazole against mucormycosis was different, and the dosage regimen needs to adjust according to fungal species.
{"title":"Pharmacokinetic/Pharmacodynamic Analysis the Probability of Target Attainment of Posaconazole against Mucorales Species in Patients with Mucormycosis","authors":"Ying Wang, Jingyi Zhao, Yinhui Yao, Junhui Hu, Jiuli Hu, Xun Xiao, Yanwu Zhao","doi":"10.4236/pp.2020.115007","DOIUrl":"https://doi.org/10.4236/pp.2020.115007","url":null,"abstract":"The objective of this study was to investigate the probability \u0000of target attainment of various posaconazole \u0000dosing regimens against Mucorales species in patients with mucormycosis. \u0000According to pharmacokinetic/pharmacodynamic parameters of posaconazole in \u0000adults, the dosage regimen of posaconazole for mucormycosis included 50, 100, 200 and 400 mg orally \u0000q12h. Monte Carlo Simulation \u0000analysed the published parameters of pharmacokinetics and the MIC values of \u0000mucormycosis in Mucorales species. The results showed that posaconazole did not affect Rhizopus arrhizus and Mucor sp. The optimal dosage of \u0000posaconazole for Rhizopus microsporus and Rhizomucor pusillus was 400 mg orally q12h and the best dosage regimen for Lichtheimia corymbifera was 200 mg orally \u0000q12h. The antifungal activity of posaconazole against mucormycosis was different, and the dosage regimen needs to \u0000adjust according to fungal species.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86769233","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}
A questionnaire survey was conducted employing pharmacists at 350 Japanese Federation of Democratic Medical Institutions (Min-Iren) member pharmacies, evaluating the challenges related to registering as a Health Support Pharmacy (HSP). Completed responses were received from 193 pharmacies (55.1%). Fifty-five (28.5%) of these pharmacies were approved as meeting the HSP criteria. Some difficulties encountered in registering as an HSP included the preparation of the numerous required documents and placing a health support pharmacist. The obstacles that prevented pharmacists from registering were physical, including “placement of two or more health support pharmacists” and “placement of the required over-the-counter drugs (OTCs).” Based on these, 51.8% of supervising pharmacists stated the opinion that the government should “loosen current criteria.” However, a survey conducted among the 724 participant pharmacists, working in a pharmacy, showed no significant difference in their answering tendencies depending on whether or not they worked at an HSP. This could be attributed to the effort that Min- Iren pharmacies have been putting into health support and primary care functions. Overall, 64.5% of pharmacists working at HSPs were proud that the pharmacy they worked had HSP status. The present survey revealed the physical obstacles of HSP registration. Conformity to the criteria of HSP is essential for performing their fundamental functions as pharmacies. The relaxation of the criteria is anticipated.
{"title":"The Japanese Community Pharmacists’ Perceptions of the Health Support Pharmacy System","authors":"N. Hirota, N. Okamura","doi":"10.4236/pp.2020.114006","DOIUrl":"https://doi.org/10.4236/pp.2020.114006","url":null,"abstract":"A \u0000questionnaire survey was conducted employing pharmacists at 350 Japanese Federation of Democratic Medical Institutions \u0000(Min-Iren) member pharmacies, evaluating the challenges related to registering \u0000as a Health Support Pharmacy (HSP). Completed responses were received from 193 \u0000pharmacies (55.1%). Fifty-five (28.5%) of these pharmacies were approved as \u0000meeting the HSP criteria. Some difficulties encountered in registering as an \u0000HSP included the preparation of the numerous required documents and placing a \u0000health support pharmacist. The obstacles that prevented pharmacists from \u0000registering were physical, including \u0000“placement of two or more health support pharmacists” and “placement of \u0000the required over-the-counter drugs (OTCs).” Based on these, 51.8% of supervising pharmacists \u0000stated the opinion that the government should “loosen current criteria.” \u0000However, a survey conducted among the 724 participant pharmacists, working in a \u0000pharmacy, showed no significant difference in their answering tendencies \u0000depending on whether or not they worked at an HSP. This could be attributed to \u0000the effort that Min- Iren \u0000pharmacies have been putting into health support and primary care functions. \u0000Overall, 64.5% of pharmacists working at HSPs were proud that the pharmacy they worked had HSP status. The present \u0000survey revealed the physical obstacles of HSP registration. Conformity \u0000to the criteria of HSP is essential for performing their fundamental functions \u0000as pharmacies. The relaxation of the criteria is anticipated.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77872359","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}
Atenolol diffusion through synthetic membrane, cloned human epidermis, and cat ear skin was performed utilizing a Franz diffusion cell. Transdermal drug diffusion enhancers’ ethanol, glycerol, propylene glycol, polysorbate 80 and Dimethyl isosorbide (DMI) were added to the topical formulations and tested for their ability to enhance drug permeation through the test membranes. Topical formulation with penetration enhancers showed a rapid burst of atenolol diffusion for the first two hours (35.5 to 40 μg/ml) followed by a zero-order sustained diffusion of 2.7 μg/cm2/h of atenolol for up to twenty-four hours after application to test membranes. Increased atenolol flux through different test membranes was greatest for synthetic membrane. The topical application of the optimized atenolol formulation to cat skin containing permeation enhancers aided transdermal atenolol drug delivery to treat cats with hypertrophic obstructive cardiomyopathy. The optimum topical formulation demonstrated two fluxes through cat skin, the burst flux (15.7 μg/cm2/h) and a sustained flux (2.7 μg/cm2/h). Measured atenolol concentrations in cats at 3, 6 and 12 hours after transdermal atenolol application were 432.7 ng/ml ± 323.3, 262.4 ng/ml ± 150.1, and 253.3 ng/ml ± 133.6 respectively. Six of 7 cats achieved therapeutic serum atenolol levels (260 ng/ml) for at least one time point. Five of 7 cats had therapeutic serum atenolol concentrations 3 hours post-atenolol. At the 6 hours post-atenolol time point, only 2 had a therapeutic serum atenolol concentration while at 12 hours post-atenolol dosing, 4 of 7 cats had therapeutic serum atenolol concentrations. Transdermal atenolol administered at 25 mg q12h resulted in clinically therapeutic serum atenolol concentrations in the majority of healthy cats. The optimum transdermal formulation enabled good drug delivery feasible for transdermal application in a clinical trial in cats.
{"title":"Transdermal Formulation Development and Topical Administration of Atenolol to Cats","authors":"Sumeia M. Mohamed, J. M. Christensen, N. Leblanc","doi":"10.4236/pp.2020.113005","DOIUrl":"https://doi.org/10.4236/pp.2020.113005","url":null,"abstract":"Atenolol diffusion through synthetic membrane, cloned human epidermis, \u0000and cat ear skin was performed utilizing a Franz diffusion cell. Transdermal drug diffusion \u0000enhancers’ ethanol, glycerol, propylene glycol, polysorbate 80 and Dimethyl \u0000isosorbide (DMI) were added to the topical formulations and tested for their \u0000ability to enhance drug permeation through the test membranes. Topical \u0000formulation with penetration enhancers showed a rapid burst of atenolol \u0000diffusion for the first two hours (35.5 to 40 μg/ml) \u0000followed by a zero-order sustained diffusion of 2.7 μg/cm2/h of atenolol for up to twenty-four hours after application to test \u0000membranes. Increased atenolol flux through different test membranes was \u0000greatest for synthetic membrane. The topical application of the optimized \u0000atenolol formulation to cat skin containing permeation enhancers aided \u0000transdermal atenolol drug delivery to treat cats with hypertrophic obstructive \u0000cardiomyopathy. The optimum topical formulation demonstrated two fluxes through \u0000cat skin, the burst flux (15.7 μg/cm2/h) and a sustained flux (2.7 μg/cm2/h). Measured atenolol concentrations in cats at 3, 6 and 12 hours after \u0000transdermal atenolol application were 432.7 ng/ml ± 323.3, 262.4 ng/ml ± 150.1, \u0000and 253.3 ng/ml ± 133.6 respectively. Six of 7 cats achieved therapeutic serum \u0000atenolol levels (260 ng/ml) for at least one time point. Five of 7 cats had \u0000therapeutic serum atenolol concentrations 3 hours post-atenolol. At the 6 hours \u0000post-atenolol time point, only 2 had a \u0000therapeutic serum atenolol concentration while at 12 hours post-atenolol \u0000dosing, 4 of 7 cats had therapeutic serum atenolol concentrations. Transdermal \u0000atenolol administered at 25 mg q12h resulted in clinically therapeutic serum \u0000atenolol concentrations in the majority of healthy cats. The optimum \u0000transdermal formulation enabled good drug delivery feasible for transdermal \u0000application in a clinical trial in cats.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"144 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79926410","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}
Dalbavancin is a novel semi-synthetic glycopeptide antibiotic. In this study, we aimed to optimize the dosage regimen of dalbavancin in patients with hepatic or renal impairment by Mote Carlo simulation. Pharmacokinetic parameters and microbiological data were collected about dalbavancin. 10,000 patients with renal or hepatic impairment analyzed by Crystal Ball to calculate probability of target attainment (PTA) and cumulative fraction of response (CFR). We found that all bacterial PTA and CFR were more than 90% for dalbavancin in patients with hepatic or renal impairment, except for Enterococcus faecium. There is no need to adjust the dosage regimen of dalbavancin in patients with hepatic or renal impairment.
{"title":"Optimization of Dalbavancin in Patients with Hepatic or Renal Impairment","authors":"Ying Wang, Jingyi Zhao, Yinhui Yao, Junhui Hu, Jiuli Hu, Xun Xiao, Yanwu Zhao","doi":"10.4236/pp.2020.112004","DOIUrl":"https://doi.org/10.4236/pp.2020.112004","url":null,"abstract":"Dalbavancin \u0000is a novel semi-synthetic glycopeptide antibiotic. In this study, we aimed to \u0000optimize the dosage regimen of dalbavancin in patients with hepatic or renal \u0000impairment by Mote \u0000Carlo simulation. Pharmacokinetic parameters and microbiological data were \u0000collected about dalbavancin. 10,000 patients with renal or hepatic impairment \u0000analyzed by Crystal Ball to calculate probability of target attainment (PTA) \u0000and cumulative fraction of response (CFR). We found that all bacterial PTA and CFR were more \u0000than 90% for dalbavancin in patients with hepatic or renal impairment, except \u0000for Enterococcus faecium. There is no need to adjust the dosage regimen of dalbavancin in \u0000patients with hepatic or renal impairment.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73804683","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}
Ying Wang, Jingyi Zhao, Junhui Hu, Xinhong Zhao, Yinhui Yao
Invasive fungal infections (IFI) have recently become increasingly more prevalent, resulting in an increased risk of morbidity and mortality. Both Candida spp. and Aspergillus spp. are major causes of IFI. In this study, we aimed to evaluate the cumulative fraction of response of various dosage regimens of posaconazole against nine Candida spp. and six Aspergillus spp. in both children and adults. Monte Carlo simulation (MCS) was performed to optimize selection of posaconazole dosage regimens. For children, a dosage regimen of 120 mg/m2 posaconazole tid was sufficient to treat fungal infections caused by all six Aspergillus spp. and six of the nine Candida spp. (but was not effective against C. glabrata, C. guilliermondii and C. krusei). In contrast, a 400 mg dosage regimen of posaconazole bid achieved the target pharmacokinetic/pharmacodynamics (PK/PD) parameters against all six Aspergillus spp. and eight of the nine Candida spp. (but was not effective against C. glabrata) in the adults. Dosage regimens of 50 mg bid, 100 mg bid, or 200 mg bid were not effective. Posaconazole dosage regimens are likely to achieve their desired PK/PD targets against Candida spp. and Aspergillus spp. in both children and adults.
侵袭性真菌感染(IFI)最近变得越来越普遍，导致发病率和死亡率的风险增加。念珠菌和曲霉菌都是IFI的主要病因。在本研究中，我们旨在评估泊沙康唑不同剂量方案对儿童和成人9种念珠菌和6种曲霉菌的累积反应分数。采用蒙特卡罗模拟(Monte Carlo simulation, MCS)优化泊沙康唑给药方案的选择。对于儿童，泊沙康唑剂量为120 mg/m2足以治疗所有6种曲霉和9种念珠菌中的6种引起的真菌感染(但对C. glabrata, C. guilliermondii和C. krusei无效)。泊沙康唑400mg给药组对6种曲霉和8种念珠菌均达到了目标药代动力学/药效学(PK/PD)参数，但对光棘球蚴无效。50mg bid, 100mg bid，或200mg bid的剂量方案均无效。泊沙康唑给药方案很可能在儿童和成人中达到对念珠菌和曲霉菌的预期PK/PD目标。
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