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  • Pharmacokinetics of omeprazole and its metabolites in three phases of menstrual cycle.

Pharmacokinetics of omeprazole and its metabolites in three phases of menstrual cycle.

European journal of drug metabolism and pharmacokinetics (2014-01-07)
Shabnam Nazir, Zafar Iqbal, Lateef Ahmad, Yasar Shah, Fazli Nasir
ABSTRACT

Omeprazole (OMP) is effective in the treatment of gastric hyperacidity and is metabolized by CYP2C19 and CYP3A4. These enzymes are modulated by estrogen and progesterone which regulate the menstrual cycle. The variations in the pharmacokinetics (PK) of many drugs like amphetamine, benzodiazepines and caffeine have been reported during menstrual cycle. In present study, the PK of the omeprazole and its metabolites was investigated during various phases of the menstrual cycle. A single oral dose, open-label, non-controlled, pharmacokinetic study of omeprazole was conducted in healthy young/premenopausal females (n = 16). The PK of omeprazole, 5-hydroxy-omeprazole and omeprazole sulphone was evaluated in three phases of menstrual cycle. The blood samples were analyzed using reversed-phase HPLC coupled with UV detector and the PK data were evaluated. The activities of CYP2C19 and CYP3A4 were determined as AUC(OH-OMP)/AUC(OMP) and AUC(OMP-SUL)/AUC(OMP), respectively. Omeprazole showed significantly (p < 0.05) higher [Formula: see text] and CL/F in follicular and menstrual phases, respectively. The [Formula: see text] of 5-hydroxy omeprazole was also significantly (p < 0.05) higher in follicular phase. The metabolic ratios (MR) of 5-hydroxy omeprazole and omeprazole sulphone were lower in follicular phase compared with the luteal phase. The present study suggests that high estrogen levels of follicular phase may result in increased absorption of omeprazole. The lower MR for 5-hydroxy omeprazole and omeprazole sulphone in follicular phase as compared to luteal phase suggests that metabolism of omeprazole is low in follicular phase as compared to luteal phase, which is progesterone-dominant phase. However, the clinical significance for these findings needs to be determined.

MATERIALS
Product Number
Brand
Product Description

Supelco
Methanol, analytical standard
Sigma-Aldrich
Methanol, anhydrous, 99.8%
Supelco
5-Hydroxyomeprazole, analytical standard
Sigma-Aldrich
Methanol, BioReagent, ≥99.93%
Sigma-Aldrich
Methanol, NMR reference standard
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Methanol, Absolute - Acetone free
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Methanol, ACS spectrophotometric grade, ≥99.9%
Sigma-Aldrich
Methanol, ACS reagent, ≥99.8%
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Methanol, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8% (GC)
USP
Omeprazole Related Compound A, United States Pharmacopeia (USP) Reference Standard
Supelco
Methanol, Pharmaceutical Secondary Standard; Certified Reference Material
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Methanol, puriss., meets analytical specification of Ph Eur, ≥99.7% (GC)
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Methanol, ACS reagent, ≥99.8%
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Methanol, Laboratory Reagent, ≥99.6%
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Methanol, ACS reagent, ≥99.8%
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Methanol, suitable for HPLC, ≥99.9%
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Methanol, suitable for HPLC, gradient grade, ≥99.9%
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Methanol, HPLC Plus, ≥99.9%
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Methanol, suitable for HPLC, gradient grade, suitable as ACS-grade LC reagent, ≥99.9%
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Potassium phosphate monobasic, 99.99% trace metals basis
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Potassium phosphate monobasic, tested according to Ph. Eur., anhydrous
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Omeprazole, solid
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Potassium phosphate monobasic, for molecular biology, ≥98.0%
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Potassium phosphate monobasic, powder, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99.0%
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Potassium phosphate monobasic, ReagentPlus®
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Potassium phosphate monobasic, BioUltra, for molecular biology, anhydrous, ≥99.5% (T)
Supelco
Omeprazole, Pharmaceutical Secondary Standard; Certified Reference Material
Omeprazole, European Pharmacopoeia (EP) Reference Standard
Supelco
Omeprazole sulfone, analytical standard
Sigma-Aldrich
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 3 mm × 8 in.