Population Pharmacokinetics of Emtricitabine in HIV-1-infected Adult Patients

Antimicrob Agents Chemother. 2014;58(4):2256-61. doi: 10.1128/AAC.02058-13. Epub 2014 Feb 3.

Abstract

The aims of this study were to describe emtricitabine concentration-time courses in a large population of HIV-1-infected adults, to evaluate the influence of renal function on emtricitabine disposition, and to assess current dosing adjustment recommendations. Emtricitabine blood plasma concentrations were determined from samples collected from 161 adult patients during therapeutic drug monitoring and measured by liquid chromatography coupled to tandem mass spectrometry. The data were analyzed by a population approach. Emtricitabine pharmacokinetics was best described by a two-compartment model in which the absorption and distribution rate constants were assumed to be equal. Typical population parameter estimates (interindividual variability) were apparent elimination and intercompartmental clearances of 15.1 liters/h (17.4%) and 5.75 liters/h, respectively, and apparent central and peripheral volumes of distribution of 42.3 liters and 55.4 liters, respectively. The apparent elimination clearance was significantly related to creatinine clearance (CLCR), reflecting renal function. For 200 mg once a day (QD), the median area under the concentration-time curve over 24 h (AUC0-24) was 12.5 mg·h/liter for patients with normal renal function (CLCR, >80 ml/min), 14.7 mg·h/liter for patients with mild renal impairment (CLCR, 79 to 50 ml/min), and 17.9 mg·h/liter for patients with moderate renal impairment (CLCR, 49 to 30 ml/min). Simulations of the recommended dosing schemes for the oral solid form of emtricitabine (i.e., 200 mg per 48 h according to renal function) led to lower emtricitabine exposures for patients with moderate renal impairment (median AUC0-48, 17.2 mg·h/liter) than for patients with normal renal function (median AUC0-48, 25.6 mg·h/liter). Administering 18 ml of emtricitabine oral solution (10 mg/ml) QD to patients with moderate renal impairment should yield emtricitabine exposures similar to those in patients with normal renal function.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / therapeutic use
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacokinetics
  • Deoxycytidine / therapeutic use
  • Emtricitabine
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism
  • Humans
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Anti-HIV Agents
  • Deoxycytidine
  • Emtricitabine