Clinical Importance of Potential Genetic Determinants Affecting Propofol Pharmacokinetics and Pharmacodynamics.

Ivana Budic,Dimitrije Pavlovic,Ivona Djordjevic,Dusica Simic,Tatjana Jevtovic Stoimenov,Vesna Marjanovic,Marija Stevic

doi:10.3389/fmed.2022.809393

Abstract

Interindividual variability in response to drugs used in anesthesia has long been considered the rule, not the exception. It is important to mention that in anesthesiology, the variability in response to drugs is multifactorial, i.e., genetic and environmental factors interact with each other and thus affect the metabolism, efficacy, and side effects of drugs. Propofol (2,6-diisopropylphenol) is the most common intravenous anesthetic used in modern medicine. Individual differences in genetic factors [single nucleotide polymorphisms (SNPs)] in the genes encoding metabolic enzymes, molecular transporters, and molecular binding sites of propofol can be responsible for susceptibility to propofol effects. The objective of this review (through the analysis of published research) was to systematize the influence of gene polymorphisms on the pharmacokinetics and pharmacodynamics of propofol, to explain whether and to what extent the gene profile has an impact on variations observed in the clinical response to propofol, and to estimate the benefit of genotyping in anesthesiology. Despite the fact that there has been a considerable advance in this type of research in recent years, which has been largely limited to one or a group of genes, interindividual differences in propofol pharmacokinetics and pharmacodynamics may be best explained by the contribution of multiple pathways and need to be further investigated.

Highlights

One of the most challenging areas of research in clinical pharmacology, pharmacy, pharmacoepidemiology, and especially pharmacogenetics is the attempt to understand why individuals respond differently to drug therapy
Genes Affecting Propofol Pharmacokinetics and Pharmacodynamics be reduced. Another major therapeutic problem is the occurrence of adverse drug events (ADEs), which is especially important in the fields of medicine where drugs of small therapeutic range are used, among which are anesthesiology and intensive care
Kanaya et al [40] found that body mass index (BMI) had an effect on propofol pharmacokinetics after a single intravenous dosage, whereas UGT1A9 and CYP2B6 SNPs, other clinical parameters, and hemodynamic variables had no effect. These findings suggested that BMI is a separate factor that influences propofol pharmacokinetics [40]

Summary

INTRODUCTION

One of the most challenging areas of research in clinical pharmacology, pharmacy, pharmacoepidemiology, and especially pharmacogenetics is the attempt to understand why individuals respond differently to drug therapy. Genes Affecting Propofol Pharmacokinetics and Pharmacodynamics be reduced Another major therapeutic problem is the occurrence of adverse drug events (ADEs), which is especially important in the fields of medicine where drugs of small therapeutic range are used, among which are anesthesiology and intensive care. Adverse drug events or overdose are responsible for nearly half of anesthesia-related deaths [2], and one out of every 20 perioperative medication doses results in an unanticipated ADE or a medication error [3]. Medications such as sedativehypnotics, inhalation and intravenous anesthetics, analgesics, and cardiovascular drugs, among others, are frequently used in perioperative treatment. Polymorphisms in cytochrome P450 (CYP) isoforms and UDP-glucuronosyltransferase (UGT), as well as drugs administered concurrently, could cause unpredictable interindividual variability of propofol pharmacokinetics and pharmacodynamics with forensic and clinically relevant adverse outcomes e.g., respiratory and cardiac depression, "propofolrelated infusion syndrome – PRIS" [8]

METHODS

Findings

CONCLUSION