Nonlinear mixed-effects model population pharmacokinetics of acetaminophen among Hausa/Fulani in Northwest Nigeria

Abstract: BACKGROUND: Acetaminophen is the most frequently used drug worldwide and the leading cause of acute liver failure in the developed world but underreported in Third World countries. The potential of acetaminophen to cause liver injury in a group of people and, therefore, the recommended safe dose schedules for that group can be predicted from population pharmacokinetics. This study aimed at determining the pharmacokinetic parameters of acetaminophen and the influence of demographic variables on the Hausa/Fulani ethnic group. MATERIALS AND METHODS: Twenty volunteers from Hausa/Fulani extractions were involved in the study through their expressed consents. It was an exploratory pharmacokinetics study. The volunteers observed an overnight fast preceding acetaminophen administration to 3-h post-administration. A single dose of acetaminophen, 1 g orally with 300 ml of distilled water, was administered. Blood sample 5 ml was collected before acetaminophen administration and 15, 30, and 45 min, and 1, 2, 3, 4, 5, and 6 h after the administration. Acetaminophen plasma concentrations were determined by validated reverse-phase high-performance liquid chromatography. MonolixSuite 2018R software was used to describe the population pharmacokinetics of the participants. RESULTS: Twenty participants were enrolled in the study, and no attrition was recorded. The age ranged from 19 to 46, with a median of 23 years. Body mass index (BMI) had an inverse relationship with plasma acetaminophen clearance when fixed effects were modeled with the covariates. Pearson’s correlation of random effects revealed a statistically significant relationship between absorption and clearance, while there was no correlation between random effects and covariates. CONCLUSION: Acetaminophen dose adjustments need to be considered with respect to BMI.