Population Pharmacokinetic/Pharmacodynamic Analysis of Nociceptive Pain Models Following an Oral Pregabalin Dose Administration to Healthy Subjects

Abstract

A battery of pain models can be used in clinical trials to investigate the efficacy and to establish the concentration‐effect relationship of novel analgesics. This study quantified the pharmacokinetics (PK) of pregabalin after a single oral dose of 300 mg and the pharmacodynamics (PD) on the pain tolerance threshold (PTT) of the cold pressor, electrical stimulation, the pressure pain model, and on the pain detection threshold of a contact heat pain model. The PK were best described using a one‐compartment model with lag time, linear absorption, and linear elimination. The PTT of the cold pressor showed a negative linear decrease over time without pregabalin. A linear drug effect was identified on the PTT of the cold pressor test and an on/off effect for the electrical stimulation PTT. No PK/PD relationship could be identified on the pressure pain and heat pain test. Citation:

Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development

“…For example, in humans, the T max of pregabalin in the cerebrospinal fluid (CSF) occurs about 8 h post dose, which indicates delayed distribution to the brain [ 57 ]. For lacosamide, the T max in plasma and CSF in humans occurs at approximately the same time [ 34 ]. Corresponding data for tapentadol have not been published.…”

“…Source: Summary of Product Characteristics and drug label. Otherwise: a Predicted using ALOGPS, Virtual Computational Chemistry Laboratory, 2005; b Chemistry review, FDA Center for Drug Evaluation and Research, application number: 22–488; c predicted using Estimation Program Interface (EPI) Suite, US EPA; d ACD/Labs; e Chemistry review, FDA Center for Drug Evaluation and Research, application number: 22–255; f May et al (2015) [ 34 ]; g Michelhaugh et al 2015 [ 35 ]; h Koo et al (2011) [ 36 ]; i Feng et al (2001) [ 37 ]; j Schröder et al (2011) [ 38 ].…”