Journal of Clinical Pharmacology最新文献_第10页

Population pharmacokinetics and pharmacodynamics of peptidic erythropoiesis receptor agonist (ERA) in healthy volunteers. 促红细胞生成受体激动剂(ERA)在健康志愿者体内的群体药动学和药效学。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2008-01-01 Epub Date: 2007-11-19 DOI: 10.1177/0091270007309702

Sukyung Woo, Wojciech Krzyzanski, Anne-Marie Duliege, Richard B Stead, William J Jusko

{"title":"Population pharmacokinetics and pharmacodynamics of peptidic erythropoiesis receptor agonist (ERA) in healthy volunteers.","authors":"Sukyung Woo, Wojciech Krzyzanski, Anne-Marie Duliege, Richard B Stead, William J Jusko","doi":"10.1177/0091270007309702","DOIUrl":"https://doi.org/10.1177/0091270007309702","url":null,"abstract":"Peptidic erythropoiesis receptor agonist is a synthetic, PEGylated peptide that can promote red blood cell production upon binding to the erythropoietin receptor. The objective of this study was to characterize the pharmacokinetics and erythropoietic effects of peptidic erythropoiesis receptor agonist in healthy volunteers. Plasma concentrations of peptidic erythropoiesis receptor agonist and pharmacodynamic responses were obtained after single intravenous injections at doses of 0.025, 0.05, and 0.1 mg/kg. Population pharmacokinetic/pharmacodynamic modeling was performed using NONMEM. Peptidic erythropoiesis receptor agonist exhibited nonlinear pharmacokinetics described by a 1-compartment model with parallel elimination by Michaelis-Menten and linear processes. A catenary, life span-based, indirect response model reflecting bone marrow erythroid and blood cells reflected the pharmacodynamics of peptidic erythropoiesis receptor agonist. A modest tolerance and rebound phenomenon in reticulocytes was modeled with negative feedback regulation related to hemoglobin. This pharmacokinetic/pharmacodynamic model well characterized the prolonged disposition, intrinsic pharmacologic parameters, and typical hematological system properties following single doses of peptidic erythropoiesis receptor agonist in normal subjects.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"48 1","pages":"43-52"},"PeriodicalIF":2.9,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270007309702","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27098673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 27

Pharmacokinetic interaction between voriconazole and efavirenz at steady state in healthy male subjects. 健康男性受试者稳定状态下伏立康唑与依非韦伦的药代动力学相互作用。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2008-01-01 Epub Date: 2007-11-19 DOI: 10.1177/0091270007309703

Ping Liu, Grover Foster, Robert R LaBadie, Maria J Gutierrez, Amarnath Sharma

{"title":"Pharmacokinetic interaction between voriconazole and efavirenz at steady state in healthy male subjects.","authors":"Ping Liu, Grover Foster, Robert R LaBadie, Maria J Gutierrez, Amarnath Sharma","doi":"10.1177/0091270007309703","DOIUrl":"https://doi.org/10.1177/0091270007309703","url":null,"abstract":"A randomized, placebo-controlled (with respect to voriconazole), 2-period, multiple-dose intragroup fixed-dose sequence study was conducted in 34 healthy male subjects to evaluate the interactions between voriconazole (triazole antifungal agent) and efavirenz (reverse transcriptase inhibitor). In period 1, subjects received 200 mg twice-daily (bid) voriconazole (n = 17) or placebo (n = 17) for 3 days (400-mg bid loading doses on day 1). In period 2, following a 7-day washout, subjects received 400 mg once-daily (qd) efavirenz alone for 10 days (days 11-20). Then efavirenz was coadministered with 200 mg bid voriconazole or placebo for the next 9 days (days 21-29). Serial plasma voriconazole and efavirenz concentrations were measured on days 3, 19, and 29, and the safety data were collected throughout the study. The 400-mg qd efavirenz dose substantially reduced the steady-state mean voriconazole area under the curve over the dosing interval (AUC0-12) by 80% (90% confidence interval [CI], 75%-84%) and peak concentration (Cmax) by 66% (90% CI, 57%-73%). The decrease in voriconazole exposure during coadministration is probably mainly due to the induction of CYP2C19 and CYP2C9 by efavirenz. The 200 mg bid voriconazole increased the steady-state mean AUC0-24 and Cmax of efavirenz by 43% (90% CI, 36%-51%) and 37% (90% CI, 29%-46%), respectively. The increase in efavirenz exposure during coadministration is probably due to the inhibition of CYP3A4 by voriconazole. Coadministration of 200 mg bid voriconazole with 400 mg (or higher) qd efavirenz is contraindicated due to the clinically significant effect of efavirenz on voriconazole pharmacokinetics.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"48 1","pages":"73-84"},"PeriodicalIF":2.9,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270007309703","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27098675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 69

Ethanol does not alter the pharmacokinetic profile of the controlled-release formulation of carvedilol. 乙醇不改变卡维地洛控释制剂的药代动力学特征。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2007-11-01 DOI: 10.1177/0091270007307244

Linda S Henderson, David M Tenero, Andrea M Campanile, Charlotte A Baidoo, Theodore M Danoff

{"title":"Ethanol does not alter the pharmacokinetic profile of the controlled-release formulation of carvedilol.","authors":"Linda S Henderson, David M Tenero, Andrea M Campanile, Charlotte A Baidoo, Theodore M Danoff","doi":"10.1177/0091270007307244","DOIUrl":"https://doi.org/10.1177/0091270007307244","url":null,"abstract":"The concomitant ingestion of alcohol may alter the release of a drug from a modified-release dosage form, posing a potential risk to patients. In a randomized, open-label, 4-period cross-over study, the pharmacokinetic profiles of R(+) and S(-) carvedilol were compared after a single oral dose of carvedilol controlled-release formulation (administered following a standard meal) was given alone or concomitantly with ethanol. Thirty-nine healthy subjects participated in this study. Following coadministration of carvedilol controlled-release 40 mg with ethanol (approximately 38 g), ethanol ingestion 2 hours before or 2 hours after carvedilol controlled-release administration, area under the curve for the R(+) and S(-) carvedilol enantiomers was similar compared with carvedilol controlled-release given alone. Carvedilol exposure was not affected by the concomitant administration of ethanol and carvedilol controlled-release. Maximum plasma concentrations for the R(+) and S(-) carvedilol enantiomers were similar except when ethanol was ingested 2 hours after carvedilol controlled-release administration, where there was a modest decrease in maximum plasma concentration for R(+) and S(-) carvedilol (16% and 17%, respectively). Carvedilol controlled-release given alone or concomitantly with ethanol ingestion was generally well tolerated, and no serious or severe adverse events were reported. Ethanol did not alter the pharmacokinetic profile of carvedilol controlled-release.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"47 11","pages":"1358-65"},"PeriodicalIF":2.9,"publicationDate":"2007-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270007307244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27070527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Evaluation of the potential for pharmacodynamic and pharmacokinetic drug interactions between selegiline transdermal system and two sympathomimetic agents (pseudoephedrine and phenylpropanolamine) in healthy volunteers. 在健康志愿者中评价舍来吉兰透皮系统与两种拟交感神经药物(伪麻黄碱和苯基丙醇胺)之间潜在的药效学和药代动力学药物相互作用。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2007-08-01 Epub Date: 2007-06-06 DOI: 10.1177/0091270007302950

Albert J Azzaro, Chad M VanDenBerg, John Ziemniak, Eva M Kemper, Lawrence F Blob, Bryan J Campbell

{"title":"Evaluation of the potential for pharmacodynamic and pharmacokinetic drug interactions between selegiline transdermal system and two sympathomimetic agents (pseudoephedrine and phenylpropanolamine) in healthy volunteers.","authors":"Albert J Azzaro, Chad M VanDenBerg, John Ziemniak, Eva M Kemper, Lawrence F Blob, Bryan J Campbell","doi":"10.1177/0091270007302950","DOIUrl":"https://doi.org/10.1177/0091270007302950","url":null,"abstract":"Selegiline transdermal system is a recently approved monoamine oxidase inhibitor antidepressant. Medications that inhibit monoamine oxidase type A can augment the pressor effects of sympathomimetic amines, increasing the potential for hypertensive crisis. This study examined the potential for drug-drug interactions during treatment with selegiline transdermal system and pseudoephedrine or phenylpropanolamine. Two studies were conducted with 25 healthy volunteers to assess changes in blood pressure and heart rate during administration of pseudoephedrine or phenylpropanolamine alone or together with selegiline transdermal system. No significant differences in mean maximum changes in vital signs occurred with pseudoephedrine. No significant differences were found in mean maximum changes in systolic heart rate with phenylpropanolamine; however, 4 of 12 subjects each experienced 1 isolated protocol-defined minimal pressor response without concurrent adverse effects (1 with phenylpropanolamine alone; 3 with phenylpropanolamine + selegiline transdermal system). Pharmacokinetic parameters obtained following selegiline transdermal system and pseudoephedrine or phenylpropanolamine were unremarkable. The results suggest that selegiline transdermal system 6 mg/24 h does not significantly alter the pharmacodynamics or pharmacokinetics of either pseudoephedrine or phenylpropanolamine when administered to healthy volunteers; however, it is prudent to avoid coadministration of selegiline transdermal system and sympathomimetics.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"47 8","pages":"978-90"},"PeriodicalIF":2.9,"publicationDate":"2007-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270007302950","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26764620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

Lopinavir/Ritonavir pharmacokinetic profile: impact of sex and other covariates following a change from twice-daily to once-daily therapy. 洛匹那韦/利托那韦药代动力学概况：从每日两次治疗改为每日一次治疗后性别和其他协变量的影响。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2007-08-01 Epub Date: 2007-07-05 DOI: 10.1177/0091270007302564

Ighovwerha Ofotokun, Susan K Chuck, Jose N Binongo, Mauricio Palau, Jeffrey L Lennox, Edward P Acosta

{"title":"Lopinavir/Ritonavir pharmacokinetic profile: impact of sex and other covariates following a change from twice-daily to once-daily therapy.","authors":"Ighovwerha Ofotokun, Susan K Chuck, Jose N Binongo, Mauricio Palau, Jeffrey L Lennox, Edward P Acosta","doi":"10.1177/0091270007302564","DOIUrl":"10.1177/0091270007302564","url":null,"abstract":"The aim of this study was to determine the impact of sex on the pharmacokinetics of lopinavir/ritonavir. Interaction between lopinavir/ritonavir and tenofovir was also evaluated. Steady-state plasma samples were obtained from virologically suppressed HIV-infected patients on lopinavir/ritonavir 800/200-mg soft gel capsule taken once daily. Drug assays were performed by high-performance liquid chromatography. Pharmacokinetic parameters estimated by noncompartmental method were reported as 90% confidence intervals (CIs) about the geometric mean ratio (GMR). There were 9 males and 11 females. No sex differences were observed in lopinavir/ritonavir pharmacokinetics profile. The GMR(sex) (women compared with men) for lopinavir area under the concentration-time curve (AUC(24)), maximum concentration (C(max)), and minimum concentration (C(min)) was 0.95 (90% CI, 0.70-1.29), 0.88 (90% CI, 0.67-1.15), and 1.27 (90% CI, 0.60-2.66), respectively. Similarly, the GMR(sex) for ritonavir AUC(24), C(max), and C(min) was 0.84 (90% CI, 0.57-1.24), 0.79 (90% CI, 0.50-1.22), and 1.02 (90% CI, 0.58-1.80), respectively. Tenofovir coadministration led to a reduction in lopinavir/ritonavir plasma exposure, giving a lopinavir GMR(tenofovir) for C(max) of 0.72 (90% CI, 0.57-0.93) and AUC(24) of 0.74 (90% CI, 0.56-0.98), respectively. No difference in lopinavir/ritonavir plasma concentrations between sexes was demonstrated in this study. However, tenofovir coadministration lowered lopinavir/ritonavir plasma exposure.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"47 8","pages":"970-7"},"PeriodicalIF":2.9,"publicationDate":"2007-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073482/pdf/nihms283169.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26816911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mesna as a nonvitamin intervention to lower plasma total homocysteine concentration: implications for assessment of the homocysteine theory of atherosclerosis. Mesna作为一种非维生素干预降低血浆总同型半胱氨酸浓度:对动脉粥样硬化同型半胱氨酸理论评估的意义。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2007-08-01 Epub Date: 2007-07-05 DOI: 10.1177/0091270007303767

Bradley L Urquhart, David J Freeman, J David Spence, Andrew A House

{"title":"Mesna as a nonvitamin intervention to lower plasma total homocysteine concentration: implications for assessment of the homocysteine theory of atherosclerosis.","authors":"Bradley L Urquhart, David J Freeman, J David Spence, Andrew A House","doi":"10.1177/0091270007303767","DOIUrl":"https://doi.org/10.1177/0091270007303767","url":null,"abstract":"Elevated plasma total homocysteine is independently associated with atherosclerosis. Recent randomized trials show that vitamins lower total homocysteine but do not prevent cardiovascular events, suggesting the need for nonvitamin therapies to evaluate whether a causative relationship exists. Mesna (sodium 2-mercaptoethanesulfonate) is a thiol-containing drug capable of liberating homocysteine bound by disulfide bonds to proteins, facilitating its excretion. The effect of oral mesna on total homocysteine has not been evaluated and was the objective of this study. Eleven healthy volunteers received vehicle or 10 mg/kg mesna in random order, after which serial blood and urine samples were collected over 4 hours. Plasma total homocysteine decreased by 24.2% (P < .0001) following mesna. Urinary homocysteine excretion was significantly greater with mesna (3.9 +/- 2.4 mumol) compared to vehicle (0.4 +/- 0.1 mumol), P < .01. Oral mesna decreases plasma total homocysteine and is a potential nonvitamin treatment for assessing the homocysteine theory of atherosclerosis.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"47 8","pages":"991-7"},"PeriodicalIF":2.9,"publicationDate":"2007-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270007303767","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26817657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16

Single- and multiple-dose administration of caspofungin in patients with hepatic insufficiency: implications for safety and dosing recommendations. 肝功能不全患者单次和多次给药卡泊芬净:安全性和剂量建议的影响

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2007-08-01 DOI: 10.1177/0091270007303764

Goutam C Mistry, Elizabeth Migoya, Paul J Deutsch, Gregory Winchell, Michael Hesney, Susan Li, Sheng Bi, Stacy Dilzer, Kenneth C Lasseter, Julie A Stone

{"title":"Single- and multiple-dose administration of caspofungin in patients with hepatic insufficiency: implications for safety and dosing recommendations.","authors":"Goutam C Mistry, Elizabeth Migoya, Paul J Deutsch, Gregory Winchell, Michael Hesney, Susan Li, Sheng Bi, Stacy Dilzer, Kenneth C Lasseter, Julie A Stone","doi":"10.1177/0091270007303764","DOIUrl":"https://doi.org/10.1177/0091270007303764","url":null,"abstract":"This report investigated safety and dosing recommendations of intravenous caspofungin in hepatic insufficiency. In the single-dose study, 8 patients each with mild and moderate hepatic insufficiency received 70 mg of caspofungin. In the multiple-dose study, 8 patients with mild hepatic insufficiency and 13 healthy matched controls received 70 mg on day 1 and 50 mg daily on days 2 through 14. Eight patients with moderate hepatic insufficiency received 70 mg on day 1 and 35 mg daily on days 2 through 14. Caspofungin was generally well tolerated with no discontinuations due to serious or nonserious adverse experiences. The area under the concentration-time profile over the interval of last quantifiable point to infinity (AUC(0-infinity)) geometric mean ratio (GMR) (90% confidence interval [CI]) for mild hepatic insufficiency/historical controls was 1.55 (1.32-1.86) in the single-dose study and for mild hepatic insufficiency/concurrent controls was 1.21 (1.04-1.39) for day 14 area under the concentration-time profile calculated over the interval 0 to 24 hours (AUC(0-24h)) following multidose. The AUC(0-infinity) GMR (90% CI) for moderate hepatic insufficiency/historical controls was 1.76 (1.51-2.06) following 70 mg; AUC(0-24h) GMR (90% CI) for moderate hepatic insufficiency/concurrent controls was 1.07 (0.90-1.28) on day 14 after 35 mg daily. No dosage adjustment is recommended for patients with mild hepatic insufficiency. A dosage reduction to 35 mg daily following the 70-mg loading dose is recommended for patients with moderate hepatic insufficiency.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"47 8","pages":"951-61"},"PeriodicalIF":2.9,"publicationDate":"2007-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270007303764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26857174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 58

Modeling of in vitro drug activity and prediction of clinical outcome in acute myeloid leukemia. 急性髓系白血病体外药物活性模型及临床预后预测。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2007-08-01 DOI: 10.1177/0091270007302563

Angelica Quartino, Mats O Karlsson, Agneta Freijs, Niclas Jonsson, Peter Nygren, Jörgen Kristensen, Elin Lindhagen, Rolf Larsson

{"title":"Modeling of in vitro drug activity and prediction of clinical outcome in acute myeloid leukemia.","authors":"Angelica Quartino, Mats O Karlsson, Agneta Freijs, Niclas Jonsson, Peter Nygren, Jörgen Kristensen, Elin Lindhagen, Rolf Larsson","doi":"10.1177/0091270007302563","DOIUrl":"https://doi.org/10.1177/0091270007302563","url":null,"abstract":"The objectives of this study were to develop a population pharmacodynamic model describing the in vitro drug sensitivity of tumor cells and to relate in vitro parameters to clinical outcome. Cell samples from 179 patients with acute myelocytic leukemia were exposed to cytosine arabinoside and daunorubicin, and cytotoxicity was analyzed using the fluorometric microculture cytotoxicity assay. A sigmoid E(max)-model for daunorubicin and an E(max)-model for cytosine arabinoside described the data. The model predicted drug potency (EC(50)) adequately from 1 concentration measurement. A logistic regression on individual in vitro parameters of 46 patients treated with the daunorubicin plus cytosine arabinoside regimen showed that the probability of complete response was significantly (P < .05) related to the product of the E(max)/EC(50) ratio of the two drugs. The findings demonstrate the value of population pharmacodynamic modeling of in vitro drug sensitivity data and a significant relationship between the in vitro parameters and clinical outcome.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"47 8","pages":"1014-21"},"PeriodicalIF":2.9,"publicationDate":"2007-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270007302563","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26857178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

Evaluation of pharmacokinetic interactions between vildagliptin and digoxin in healthy volunteers. 评价维格列汀和地高辛在健康志愿者体内的药代动力学相互作用。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2007-08-01 DOI: 10.1177/0091270007301802

Yan-Ling He, Ron Sabo, Gangadhar Sunkara, Marie-Noëlle Bizot, Gilles-Jacques Riviere, Selene Leon, Monica Ligueros-Saylan, William P Dole, Dan Howard

{"title":"Evaluation of pharmacokinetic interactions between vildagliptin and digoxin in healthy volunteers.","authors":"Yan-Ling He, Ron Sabo, Gangadhar Sunkara, Marie-Noëlle Bizot, Gilles-Jacques Riviere, Selene Leon, Monica Ligueros-Saylan, William P Dole, Dan Howard","doi":"10.1177/0091270007301802","DOIUrl":"https://doi.org/10.1177/0091270007301802","url":null,"abstract":"Vildagliptin is a novel antidiabetic agent that is an orally active, potent, and selective inhibitor of dipeptidyl peptidase IV, the enzyme responsible for degradation of the incretin hormones. This open-label, randomized, 3-period crossover study investigated the potential for pharmacokinetic interactions in 18 healthy subjects during coadministration of vildagliptin and digoxin. Subjects were randomized to receive each of 3 treatments: vildagliptin 100 mg qd, digoxin (0.5 mg, then 0.25 mg qd on days 2-7), and the combination vildagliptin/digoxin for 7 days. Coadministration of digoxin with vildagliptin had no effect on exposure to vildagliptin (geometric mean ratios [90% confidence interval]: AUC(0-24h), 0.99 [0.95-1.03]; C(max), 0.95 [0.85-1.06]) or to digoxin (AUC(0-24h), 1.02 [0.94-1.12]; C(max), 1.08 [0.97-1.20]). In addition, no changes in t(max), t((1/2)), and CL/F were observed for either drug. These results indicate that no dose adjustment is necessary when vildagliptin and digoxin are coadministered.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"47 8","pages":"998-1004"},"PeriodicalIF":2.9,"publicationDate":"2007-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270007301802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26857176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 41

Renal safety and pharmacokinetics of ibandronate in multiple myeloma patients with or without impaired renal function. 依班膦酸盐在伴有或不伴有肾功能损害的多发性骨髓瘤患者中的肾脏安全性和药代动力学。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2007-08-01 Epub Date: 2007-07-05 DOI: 10.1177/0091270007301801

Raoul Bergner, Dirk M Henrich, Martin Hoffmann, Andrea Honecker, Gerd Mikus, Bettina Nauth, Dietmar Nagel, Michael Uppenkamp

{"title":"Renal safety and pharmacokinetics of ibandronate in multiple myeloma patients with or without impaired renal function.","authors":"Raoul Bergner, Dirk M Henrich, Martin Hoffmann, Andrea Honecker, Gerd Mikus, Bettina Nauth, Dietmar Nagel, Michael Uppenkamp","doi":"10.1177/0091270007301801","DOIUrl":"https://doi.org/10.1177/0091270007301801","url":null,"abstract":"In this open-label study, the authors assessed the pharmacokinetics and safety of ibandronate in patients with multiple myeloma and varying renal function. Renal deterioration was graded at baseline depending on creatinine clearance in 4 stages (0: >80; 1: 50-79; 2: 30-49, and 3: <30 mL/min). Patients (n = 40) received intravenous ibandronate 6 mg (30-minute infusion). Ibandronate excretion and serum levels were measured over 24 hours. Serum creatinine, creatinine clearance, and markers of tubular damage were monitored before ibandronate infusion and at 24 and 72 hours following ibandronate infusion. Ibandronate clearance, AUC(0-24), AUC(0-infinity), serum t((1/2)), and C(max) were calculated. There was a significant positive correlation between ibandronate clearance and creatinine clearance (r = 0.858; P < .00001). The AUC for grade 3 renal insufficiency increased by approximately 60% versus grade 0 (P < .01) but was not significantly different between other grades of renal function. The t((1/2)) did not increase significantly, and peak serum levels of ibandronate were similar for the 4 grades of renal function. Serum creatinine, creatinine clearance, and markers of tubular damage did not change significantly within 72 hours of ibandronate infusion. Despite renal function already being compromised in this patient group, there was no evidence of acute nephrotoxicity with ibandronate.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":"47 8","pages":"942-50"},"PeriodicalIF":2.9,"publicationDate":"2007-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0091270007301801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26818105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 37