Pharmacokinetic variability of phenobarbital: a systematic review of population pharmacokinetic analysis
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REVIEW
Pharmacokinetic variability of phenobarbital: a systematic review of population pharmacokinetic analysis Janthima Methaneethorn 1,2
&
Nattawut Leelakanok 3
Received: 17 April 2020 / Accepted: 1 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Aims and background Population pharmacokinetics with Bayesian forecasting provides for an effective approach when individualized drug dosing, while phenobarbital is a narrow therapeutic index drug that requires therapeutic drug monitoring. To date, several population pharmacokinetic models have been developed for phenobarbital, these showing a number of significant predictors of phenobarbital clearance and volume of distribution. We have therefore conducted a systematic review to summarize how these predictors affect phenobarbital pharmacokinetics as well as their relationships with pharmacokinetic parameters. Method A systematic search for studies of phenobarbital population pharmacokinetics that were carried out in humans and that employed a nonlinear mixed-effect approaches was made using the PubMed, Scopus, CINAHL Complete, and ScienceDirect databases. The search covered the period from these databases’ inception to March 2020. Results Eighteen studies were included in this review, all of which used a one-compartment structure. The estimated phenobarbital clearance and volume of distribution ranged from 0.0034 to 0.0104 L/h/kg and 0.37 to 1.21 L/kg, respectively, with body weight, age, and concomitant antiepileptic drugs being the three most frequently identified predictors of clearance. Most models were validated through the use of an advanced internal approach. Conclusion Phenobarbital clearance may be predicted from previously developed population pharmacokinetic models and their significant covariate-parameter relationships along with Bayesian forecasting. However, when applying these models in a target population, an external evaluation of these models using the target population is warranted, and it is recommended that future research be conducted to investigate the link between population pharmacokinetics and pharmacodynamics. Keywords Phenobarbitone . Phenobarbital . Population pharmacokinetics . Systematic review . Nonlinear mixed-effect
Background Phenobarbital, a conventional antiepileptic drug (AED), is commonly used for the treatment of generalized and partial Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00228-020-03011-x) contains supplementary material, which is available to authorized users. * Janthima Methaneethorn [email protected] 1
Pharmacokinetic Research Unit, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand
2
Center of Excellence for Environmental Health and Toxicology, Naresuan University, Phitsanulok, Thailand
3
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand
seizures, and though its use has declined in fa
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