Cytochrome P450 polymorphisms in geriatric patients - Impact on adverse drug reactions - A pilot study

Background and objective: Up to 23% of the population, depending on their ethnic background, has genetically determined differences in the metabolism of drugs by the cytochrome P450 (CYP) enzymes CYP2C9, CYP2C19 and CYP2D6. The aim of this survey was to determine the relationship between genetical polymorphisms in these CYP enzymes and adverse drug reactions (ADRs) in geriatric patients. Study design: In a prospective 6-month cohort study of 243 patients in a geriatric rehabilitation ward, mean age 80.2 +/- 7.7 years, ADRs were identified by intensive monitoring by a pharmacoepidemiological team, consisting of pharmacists and physicians. 125 out of these 243 patients were genotyped cross-sectionally for polymorphisms of CYP2C9, CYP2C19 and CYP2D6 by the TaqMan-polymerase chain reaction. The main outcome measures were the prevalence of genetical polymorphisms and the patients' risk for developing an ADR as related to the genotype. Results: Patients received an average of 14.2 drugs during hospitalisation which led to 251 ADRs in the whole cohort and 149 ADRs in the cross-sectional genotyping study. Genotype frequencies of CYP2C9 enzyme were 25.9% (n = 29) intermediate metabolisers (IMs) and 2.7% (n = 3) poor metabolisers (PMs). For the enzyme CYP2C19,26.8% (n = 33) IMs and 0.8% (n = 1) PMs were detected. For the enzyme CYP2D6, 24.1% (n = 26) IMs and 3.7% (n = 4) PMs were found in the analysed patient population. In total, 61.6% (n = 77) of genotyped patients experienced mutations in at least one of the three cytochrome enzymes. The ADR rate did not differ significantly between patients with genetic mutations and wild-type genotype patients. Moreover, only eight out of 40 ADRs which were associated with drugs metabolised by CYP2C9, CYP2C19 or CYP2D6 were detected in patients with IM genotype and none in patients with PM genotype. Conclusion: In this investigation geriatric patients showed a high rate of ADRs. However, no association between the ADR rate and the patients' genotype could be detected, which most likely was a result of the small number of patient samples analysed. Although prophylactic genotyping would have not prevented ADRs in this pilot study, physicians nevertheless have to be aware of potential genetic mutations in patients with polypharmacy.