2011 - Athens - Greece

PAGE 2011: Model evaluation
Namyi Gu

Population Pharmacokinetics of a new TRPV1 antagonist in healthy volunteers.

Namyi Gu, Bo-Hyung Kim, SeungHwan Lee, Min Kyu Park, Donghoon Shin, In-Jin Jang, Kyung-Sang Yu

Department of Clinical Pharmacology and Therapeutics, Seoul National University and Hospital, Seoul, Republic of Korea

Objectives: The transient receptor potential cation channel subfamily V member 1 (TRPV1) is reported to be involved in the transmission and modulation of pain. Drug X is a TRPV1 antagonist for analgesic treatment currently under clinical investigation. This work aimed to investigate population pharmacokinetics of drug X in healthy volunteers.

Methods: Ninety-seven volunteers had been orally administered single or multiple doses of Drug X ranging from 10 mg to 600 mg in two randomized, placebo-controlled, ascending dose studies. The 1908 plasma concentrations-time points were used to analyze the population pharmacokinetics with NONMEM VI. The demographic and laboratory data were screened as covariate of pharmacokinetic parameters.

Results: The model was composed of 4 compartments (absorption, central, peripheral and gallbladder) with first-order absorption and enterohepatic recycling. The gallbladder emptying was added twice a day after lunch and dinner[1]. The population typical estimates of clearance and volume of distribution with its relative standard errors were 5.6 L/h (6.4%) and 35 L (10.3%) in the central compartment. The typical intercompartment clearance and peripheral distribution volume were 16 L/h (9.7%) and 122 L (7.4%). Body weight, daily administered dosage and serum albumin level were selected as covariates of pharmacokinetic parameters; body weight for central and intercompartment clearances and peripheral distribution volume, dose in a day for central volume and intercompartment clearance, serum albumin level for central distribution volume.

Conclusions: This population pharmacokinetic model may produce beneficial information in designing further clinical trials along the drug development process.

[1] Zheng Jiao et al., Br J Clin Pharmacol. 2008 Jun;65(6):893-907

Reference: PAGE 20 (2011) Abstr 2139 [www.page-meeting.org/?abstract=2139]
Poster: Model evaluation