Ultrarapid Drug Metabolism and Antidepressant Failures: A Study on the CYP2C19*17 Allele

Strategic Insights -

Researchers from Karolinska University in Stockholm, Sweden, have investigated the association between ultrarapid drug metabolism and therapeutic failures of antidepressants. According to their study, published in the European Journal of Clinical Pharmacology, the CYP2C19*17 allele is linked to higher levels of CYP2C19 gene transcription and increased metabolism rates of omeprazole and mephenytoin. The researchers aimed to compare the impact of the CYP2C19*17 allele on omeprazole single-dose kinetics with escitalopram exposure at steady state in volunteers genotyped as either CYP2C19*17/*17 or CYP2C19*1/*1.

Key Takeaways:

  • The CYP2C19*17 allele is associated with higher levels of CYP2C19 gene transcription and increased rates of omeprazole and mephenytoin metabolism.
  • In the study, 16 healthy volunteers participated, five homozygous for CYP2C19*17 and 11 homozygous for CYP2C19*1.
  • Individual pharmacokinetic parameters were determined after single-dose omeprazole of 40 mg and after 1 week on escitalopram 5 mg b.i.d.
  • Escitalopram area under the concentration time curve from zero to 12 h (AUC(0-12h)) was 21% lower in homozygous carriers of CYP2C19*17 compared with CYP2C19*1 (p=0.08).
  • There was a significant correlation between escitalopram exposure at steady state and the single-dose kinetics of omeprazole (Spearman correlation coefficient of 0.67; p=0.006).
  • The study concluded that a clinically significant difference in escitalopram or omeprazole kinetics between the genotypes appears unlikely.

Statistics:

  • 16 healthy volunteers participated in the study.
  • Five participants were homozygous for CYP2C19*17, and 11 were homozygous for CYP2C19*1.
  • The escitalopram area under the concentration time curve from zero to 12 h (AUC(0-12h)) was 21% lower in homozygous carriers of CYP2C19*17 compared with CYP2C19*1.
  • The Spearman correlation coefficient between escitalopram exposure at steady state and the single-dose kinetics of omeprazole was 0.67 (p=0.006).

Sources:

  • S.O. Rosenborg, et al. "Kinetics of omeprazole and escitalopram in relation to the CYP2C19*17 allele in healthy subjects." European Journal of Clinical Pharmacology, 2008;64(12):1175-1179.
  • S.O. Rosenborg, Karolinska University Hospital Huddinge, Division Clinic Pharmacology, Dept. of Laboratory Medical, Karolinska Institute, SE-14186 Stockholm, Sweden.