Pharmacokinetics of medroxyprogesterone acetate after single and multiple injection of cyclofem® in Chinese women

• Published in: Contraception (Stoneham) 1998-06, Vol.57 (6), p.405-411
• Main Authors: Zhou, Xiao-fei, Shao, Qing-xiang, Han, Xue-jun, Weng, Li-ju, Sang, Guo-wei
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Birth control; Contraceptive Agents, Female; Contraceptives, Oral, Combined - administration & dosage; Contraceptives, Oral, Combined - pharmacokinetics; Cyclofem; estradiol; Estradiol - administration & dosage; Estradiol - analogs & derivatives; Estradiol - blood; Estradiol - pharmacokinetics; Female; Gynecology. Andrology. Obstetrics; Hormonal contraception; Humans; Injections, Intramuscular; Kinetics; Medical sciences; medroxyprogesterone acetate; Medroxyprogesterone Acetate - administration & dosage; Medroxyprogesterone Acetate - blood; Medroxyprogesterone Acetate - pharmacokinetics; monthly injectable contraceptive; pharmacokinetics; Population
• ISSN: 0010-7824; 1879-0518
• DOI: 10.1016/S0010-7824(98)00048-1

To provide pharmacokinetic data for safety evaluation on prolonged treatment with Cyclofem®, which contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate in 0.5 mL microcrystalline aqueous suspension, the pharmacokinetic profiles of MPA after single and multiple administration of this monthly injectable contraceptive were investigated in Chinese women. Nine healthy fertile women received Cyclofem based on a once-a-month regimen for up to 1 year. Blood samples were collected immediately prior to drug administration and on days 1, 3, 5, 7, 14, 21, and 28 after injection. After the 1st, 6th, and 12th injection, the maximum serum concentrations (C max) of MPA were observed on days 3.4 ± 0.9, 4.3 ± 2.2, and 3.7 ± 2.6, respectively. C max of serum MPA during the 1st, 6th, and 12th treatment cycles were 3.75 ± 1.27, 5.54 ± 1.79, and 5.55 ± 1.80 nmol/L, whereas the areas under the curve (AUC 0–28 days) were 55.84 ± 28.15, 95.45 ± 26.56, and 98.81 ± 21.84 nmol/L·day, respectively. There was significant interindividual variation in the pharmacokinetics of MPA after intramuscular injection of Cyclofem. No significant change was demonstrated in mean residence time (MRT) of MPA after single and multiple injection. There was a tendency of increase in C max and AUC 0–28 days of MPA during the first 6 months of treatment, whereas no further enhancement was found between the 6th and 12th injection (p > 0.05). Peak levels of estradiol (E 2) observed in Cyclofem users were within the normal range of the preovulatory phase. Results of this long-term study suggest that no drug accumulation occurred after repeated administration of Cyclofem in the Chinese women.