title: Pharmacokinetics of omeprazole and its metabolites in three phases of menstrual cycle.
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.
authors.affiliation: Kohat University of Science and Technology, Kohat, KPK, Pakistan, shabnammunirmalik@yahoo.com.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Nazir
authors.forename: Zafar
authors.initials: Z
authors.lastname: Iqbal
authors.forename: Lateef
authors.initials: L
authors.lastname: Ahmad
authors.forename: Yasar
authors.initials: Y
authors.lastname: Shah
authors.forename: Fazli
authors.initials: F
authors.lastname: Nasir
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood / Q000493:pharmacokinetics; D000284:Administration, Oral; D019540:Area Under Curve; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D065731:Cytochrome P-450 CYP2C19 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D005260:Female; D005498:Follicular Phase / Q000097:blood; D064368:Healthy Volunteers; D006801:Humans; D008183:Luteal Phase / Q000097:blood; D008597:Menstrual Cycle / Q000097:blood; D008598:Menstruation / Q000097:blood; D008657:Metabolic Clearance Rate; D009853:Omeprazole / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; C040450:omeprazole sulfone; C049963:5-hydroxymethylomeprazole; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009853:Omeprazole