Open AccessPopulation Pharmacokinetic/Pharmacodynamic Analysis of Nociceptive Pain Models Following an Oral Pregabalin Dose Administration to Healthy Subjects
Author(s) -
Esdonk Michiel J.,
Lindeman Ian,
Okkerse Pieter,
Kam Marieke L.,
Groeneveld Geert J.,
Stevens Jasper
Publication year - 2018
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12318
Subject(s) - pregabalin , pharmacodynamics , medicine , cold pressor test , anesthesia , pharmacokinetics , threshold of pain , nociception , population , pain tolerance , analgesic , pharmacology , blood pressure , receptor , heart rate , environmental health
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.