A phase I/II study evaluating the pharmacokinetics, pharmacodynamics, and safety of drospirenone as an oral contraceptive in Japanese women.

AIM: Drospirenone (DRSP) is a synthetic progestogen approved as a progestin-only pill for contraception in both the United States and Europe. Herein, we conducted a phase I/II study to evaluate the pharmacokinetics, pharmacodynamics, and safety of DRSP in Japanese women. METHODS: Single and multiple doses of 4 mg of DRSP were orally administered to healthy premenopausal Japanese women. In the multiple-dose period, 4 mg of DRSP was administered once daily for 24 days. Pharmacokinetics, hormone levels, and adverse events (AEs) were investigated. RESULTS: Twelve Japanese women participated in this study. The single- and multiple-dose pharmacokinetics of DRSP was similar to that reported in previous studies in Caucasians. In the multiple-dose period, no subject displayed a progesterone level of more than 5.03 ng/mL. AEs were observed in 11 (91.7%) subjects. The most common AE was genital hemorrhage, which was observed in six (50.0%) subjects, followed by diarrhea and acne in four (33.3%) subjects each. All AEs resolved or improved at the end of the study, and complete recovery was confirmed in all subjects at follow-up. CONCLUSIONS: The pharmacokinetics of DRSP in Japanese women was similar to that of previous studies performed in Caucasian women. Repeated administration of DRSP maintained low plasma progesterone levels indicating effective inhibition of ovulation. No notable safety concerns were observed. In this phase I/II study, DRSP had no obvious pharmacokinetic, pharmacodynamic, or safety issues to consider in Japanese women.

Pharmacokinetics of the H(2) blocker roxatidine acetate hydrochloride in pediatric patients, in comparison with healthy adult volunteers.

Clinical studies were conducted to investigate the pharmacokinetics of roxatidine acetate hydrochloride capsules (ALTAT(®) CAPSULES) in children. In a single-dose pharmacokinetic (PK) study in pediatric patients aged between 6 and 14 years with acid-related diseases, 37.5 mg or 75 mg roxatidine capsules were given orally, and blood samples were collected to determine the plasma roxatidine concentrations. Meanwhile, a single-dose PK study in healthy adult volunteers was newly conducted; subjects were given 37.5 mg, 75 mg or 150 mg roxatidine capsules. Differences were present between the PK parameters in pediatric patients and those in healthy adult volunteers. However, the CL/F and Vd/F adjusted by body surface area (BSA) or body weight (BW) were comparable. A close correlation of the C(max) and AUC(0-∞) to the dose per unit BSA (mg/m(2)) or BW (mg/kg) was also shown. In the multiple-dose study in pediatric patients, no roxatidine accumulation in plasma was observed, as was the case with a previous study in adults. These data show that the PK profile of roxatidine in pediatric patients is similar to the profile in healthy adult volunteers when adjusted by BSA or BW.