Activity of CYP3A4 and CYP2C19 in Young Women Who Use Depot Medroxyprogesterone Acetate (DMPA) [23N]

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Abstract

INTRODUCTION:

Cytochrome P450 enzymes (CYPs) affect concentrations of pharmaceutical agents. CYP3A4 metabolizes DMPA, and its activity is regulated by sex steroids. Metabolites of omeprazole (OMP) can be used as biomarkers to characterize activity of CYP3A4 and CYP2C19, another CYP involved in drug metabolism. OMP is metabolized by CYP3A4 to omeprazole-sulphone (SOMP) and by 2C19 to 5-hydroxyomeprazole (HOMP). These biomarkers are noninvasive means to examine effects of DMPA on CYP3A4 and 2C19.

METHODS:

This was an open-label, nonrandomized, prospective trial with Institutional Review Board approval. 20 female participants aged 18–24 years underwent an overnight fast prior to ingesting 20 mg omeprazole. Blood was collected prior and three hours later. Plasma was analyzed for omeprazole, omeprazole-sulphone, and 5-hydroxyomeprazole by high pressure liquid chromatography. Subjects then received 150 mg DMPA intramuscularly. Omeprazole test was repeated at four and twelve weeks.

RESULTS:

Nineteen participants completed. For CYP3A4, mean ratio of SOMP/OMP from baseline to four weeks decreased 0.556 to 0.495 (two-tailed P=.352, 95% CI −0.0718 to 0.1818), and baseline to 12 weeks decreased 0.551 to 0.445 (P=.197, 95% CI −0.1447 to 0.3291). These differences are not statistically significant. The HOMP/OMP change from baseline to four weeks increased 0.691 to 0.746 (P=.739, 95% CI −0.3692 to 0.2692), and baseline to 12 weeks increased 0.662 to 0.722 (P=.840, 95% CI −0.6330 to 0.5341). These do not reflect a significant change in CYP2C19 activity.

CONCLUSION:

Polymorphisms in phenotypic activity of CYPs may affect response to inducers. There was no significant alteration in CYP3A4/2C19 activity induced by DMPA. This is important as these enzymes are involved in metabolism of DMPA and estradiol.

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