Taegon Hong (1,2), Seunghoon Han (1,2), Jongtae Lee (1,2), Sangil Jeon (1,2), Jeongki Paek (1,2), Dong-Seok Yim (1,2)
(1) Department of Pharmacology, College of Medicine, The Catholic University of Korea, (2) Department of Clinical Pharmacology and Therapeutics, Seoul St.Mary's Hospital
Objectives: Pregabalin is an anticonvulsant used for the treatment of neuropathic pain and partial seizure in adults. The aim of this study was to develop a population pharmacokinetic (PK) model to describe the absorption characteristics of pregabalin given fasting or after meals.
Methods: Data from 5 healthy subject PK studies (n = 88) of single or multiple dose pregabalin (150 mg) were used. Pregabalin was administered twice daily, without meals or 30 min after a meal (regular diet or high fat diet) in the morning and 30 min or 4 h after a meal (regular diet) in the evening. Serial plasma samples were collected up to 24 h after the last dose for PK analysis. To find the model that best describes the absorption process, first-order, transit compartment, and Weibull-type absorption models were compared using the non-linear mixed effect method (NONMEM, ver. 7.2).
Results: A two-compartment linear PK model with Weibull-type absorption using its cumulative distribution function was better than the first-order absorption model with lag time. The conditional weighted residuals at Tmax and visual predictive check plots obtained from the Weibull-type absorption model were less biased than those from the first-order absorption model.
Conclusions: We found that the Weibull-type absorption model best described the absorption characteristics of pregabalin regardless of meal status and the absorption model should be carefully chosen based upon the principle of model development and validation, not by following a conventional model for its popularity and simplicity, especially when the PK dataset includes densely sampled data.
References:
[1] Bockbrader HN, Radulovic LL, Posvar EL, Strand JC, Alvey CW, Busch JA, Randinitis EJ, Corrigan BW, Haig GM, Boyd RA, Wesche DL. Clinical pharmacokinetics of pregabalin in healthy volunteers. J Clin Pharmacol. 2010 Aug;50(8):941-950
Reference: PAGE 22 () Abstr 2817 [www.page-meeting.org/?abstract=2817]
Poster: Absorption and Physiology-Based PK