Genotyping consists of determining the patient DNA sequence and analyzing functional genetic variants coding for specific enzymes. Their activity can be predicted by genotyping and/or measured by phenotyping. Cytochromes P450 (CYP450) are among the most studied enzymes from a pharmacokinetic point of view. Pharmacokinetic variability is a major source of differences in drug response and can be due to genetic variants, diseases themselves and/or DDI. Variability in drug response can affect pharmacokinetics, pharmacodynamics, or both ( Roden et al., 2019). Several causes of variability can be cited, genetic- or disease-related changes in drug concentrations or responsiveness, poor compliance, drug-drug interactions (DDI). A dose that is effective in a given patient may cause an adverse drug reaction (ADR) in another patient or conversely be ineffective. Patients vary in their response to drugs. Genotype and/or phenotype results explained or at least contributed to the clinical event in 44% of cases. Inefficacy (or low drug levels) and adverse drug reaction (or high drug levels) were the main reasons for testing. In the 537 patients, the majority of clinical situations were observed with analgesic/anesthetic drugs ( n = 187), followed by antidepressants ( n = 153), antineoplastics ( n = 97), and immunosuppressants ( n = 93). Therefore genotyping and phenotyping tests are complementary approaches when aiming to individualize drug therapy. Discrepancies between the phenotype predicted on the basis of genotyping and the measured phenotype were not always explained by concurrent medication (phenotypic switch). Genotyping correctly predicted poor metabolizer phenotypes for most CYPs isoenzymes studied, whereas agreement was more variable for intermediate, normal, and ultrarapid metabolizers. A total of 537 patients were genotyped and/or phenotyped for CYP450 during this period, and 241 underwent simultaneous genotyping and phenotyping allowing for genotype/phenotype concordance assessment. The prospectively collected data from patients who were genotyped and/or phenotyped between January 2014 and December 2020 were reviewed. Our study aims to report the concordance between CYP450 genotype and phenotype in real-life patients. Since its clinical implementation, it has been used in approximately 500 patients in various clinical situations.
In 2014, the Geneva cocktail using dried blood spots was validated in healthy volunteers for CYP450 phenotyping. Depending on the presence of drugs and/or diseases that can affect their in vivo activity, both approaches can be complementary. Their activity can be measured by phenotyping, and/or predicted by genotyping. Cytochromes P450 are among the most studied enzymes from a pharmacokinetic point of view. Pharmacokinetic variability is a major source of differences in drug response and can be due to genetic variants and/or drug-drug interactions. Division of Clinical Pharmacology and Toxicology, Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University Hospitals of Geneva, Geneva, Switzerland.Kuntheavy Ing Lorenzini* Jules Desmeules Victoria Rollason Stéphane Bertin Marie Besson Youssef Daali Caroline F.
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