Population pharmacokinetics of dolutegravir in HIV‐infected treatment‐naive patients
| Autor: | Ilisse Minto, Brian M. Sadler, Jianping Zhang, Steve Piscitelli, Ivy Song, Sherene Min, Siobhan Hayes, Julie Brandt |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Oncology medicine.medical_specialty Pyridones Population Integrase inhibitor HIV Infections Pharmacology Emtricitabine Models Biological Piperazines chemistry.chemical_compound Pharmacokinetics population pharmacokinetics Abacavir Internal medicine Oxazines Humans Medicine Computer Simulation Clinical Trials Pharmacology (medical) HIV Integrase Inhibitors education Randomized Controlled Trials as Topic Volume of distribution education.field_of_study business.industry treatment-naive integrase inhibitor Lamivudine Healthy Volunteers dolutegravir chemistry Area Under Curve Dolutegravir business Heterocyclic Compounds 3-Ring medicine.drug |
| Zdroj: | British Journal of Clinical Pharmacology |
| ISSN: | 1365-2125 0306-5251 |
| DOI: | 10.1111/bcp.12639 |
| Popis: | Aim Dolutegravir is the newest integrase inhibitor approved for HIV treatment and has demonstrated potent antiviral activity in patient populations with a broad range of treatment experience. This analysis aimed to characterize the population pharmacokinetics of dolutegravir in treatment-naive patients and to evaluate the influence of patient covariates. Methods A population pharmacokinetic model was developed using a non-linear mixed effect modelling approach based on data from 563 HIV-infected, treatment-naive adult patients in three phase 2/3 trials who received dolutegravir (ranging from 10–50 mg once daily) alone or in combination with abacavir/lamivudine or tenofovir/emtricitabine. Results The pharmacokinetics of dolutegravir were adequately described by a linear one compartment model with first order absorption, absorption lag time and first order elimination. Population estimates for apparent clearance, apparent volume of distribution, absorption rate constant and absorption lag time were 0.901 l h–1, 17.4 l, 2.24 h−1, and 0.263 h, respectively. Weight, smoking status, age and total bilirubin were predictors of clearance, weight was a predictor of volume of distribution and gender was a predictor of bioavailability. However, the magnitude of the effects of these covariates on steady-state dolutegravir plasma exposure was relatively small ( |
| Databáze: | OpenAIRE |
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