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.

Pharmacokinetics, Bioequivalence, and Safety Studies of Pantoprazole Sodium Enteric‐Coated Tablets in Healthy Subjects

“…In addition, modulation of CYP2C19 and CYP3A4 is influenced by estrogen and progesterone, which regulate the menstrual cycle. According to a previous study, high estrogen levels in the follicular phase may result in increased absorption of omeprazole 18 …”

“…According to a previous study, high estrogen levels in the follicular phase may result in increased absorption of omeprazole. 18 Filipe's 19 study stated that it should be noted that the sampling scheme was adequate for AUC and C max characterization. In suboptimal sampling schedules, missing C max estimations of the ratio could be affected, and thus variability may be higher.…”

Prediction of the Area under the Curve Using Limited-Point Blood Sampling in a Cocktail Study to Assess Multiple CYP Activities

“…In clinical settings, the wide variability of pharmacokinetics shown as wide range of clearance are observed due to various factors such as disease, age, and concomitant medications. 1,5,20,21) It is likely that the prediction models for applying the populations with a wide range of clearance could be useful for both in clinical settings and the development of medicines. However, usual clinical pharmacokinetic studies were conducted on healthy subjects, and the range of clearance in these subjects would be narrow.…”

Studies on CYP3A activity during the menstrual cycle as measured by urinary 6β‐hydroxycortisol/cortisol

“… 8 , 9 , 10 Regarding investigations of potential menstrual cycle variability in endogenous markers of CYP3A, studies are sparse and the results are difficult to interpret due to methodological issues. 9 , 10 , 11 , 12 , 13 , 14 One of the endogenous markers used to detect CYP3A activity is the 6β‐OH‐cortisol/cortisol (6β‐OHC/C) ratio in urine since cortisol is a substrate for CYP3A. 15 The advantage with 6β‐OHC/C is its short half‐life that can detect rapid changes in CYP3A activity.…”