The possible role of enterohepatic cycling on bioavailability of norethisterone and gestodene in women using combined oral contraceptives

• Published in: Contraception (Stoneham) Vol. 63; no. 1; pp. 13 - 18
• Main Authors: Elomaa, Kaisa, Ranta, Sirpa, Tuominen, Juhani, Lähteenmäki, Pekka
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2001; Elsevier Science
• Subjects: Adult; Biological and medical sciences; Biological Availability; Birth control; Charcoal; Charcoal - pharmacology; Combined oral contraceptive; Contraceptives, Oral, Combined - pharmacokinetics; Enterohepatic circulation; Enterohepatic Circulation - drug effects; Enterohepatic Circulation - physiology; Ethinyl Estradiol - administration & dosage; Ethinyl Estradiol - pharmacokinetics; Female; Finland; Gynecology. Andrology. Obstetrics; Hormonal contraception; Humans; Medical sciences; Norethindrone - administration & dosage; Norethindrone - pharmacokinetics; Norpregnenes - administration & dosage; Norpregnenes - pharmacokinetics; Pharmacokinetics; Progestogens; Finland; Progestogens; Combined oral contraceptive; Pharmacokinetics; Enterohepatic circulation; Charcoal; Ethinylestradiol; Human; Drug combination; Estrogen; Oral administration; Antidiarrheal agent; Bioavailability; Enterohepatic cycle; Progestagen; Gestodene; Activated carbon; Female; Contraceptive; Drug interaction; Norethisterone; Comparative study
• ISSN: 0010-7824; 1879-0518
• DOI: 10.1016/S0010-7824(00)00195-5

Using steady-state conditions we aimed to test if administration of oral activated charcoal affects the bioavailability of norethisterone acetate (NET Ac) and gestodene (GEST) by inhibiting their enterohepatic recirculation. Thirteen volunteers received, in a randomized order, Minulet ® (75 μg GEST and 30 μg ethinylestradiol [EE 2]) and Econ/30 ® (1 mg NET Ac and 30 μg EE 2), each for 4 months. Serum GEST and norethisterone (NET) levels were evaluated with respect to C max, t max and 24-h area under the curve (AUC 0–24h) in the middle of the control (3rd) cycle and the charcoal treatment (4th) cycle during both pill treatments. No statistically significant difference was seen in any of the aforementioned variables between the control and charcoal treatment cycles of either pill. Neither was a difference seen in the bioavailability of GEST and NET as evaluated by the ratios of two 24-h AUCs calculated in the control and charcoal cycles of each pill treatment (p = 0.29). The results suggest that enterohepatic circulation of GEST and NET is not of clinical importance. We conclude that women on oral contraceptives can take activated charcoal for the treatment of diarrhea when administered 3 h after and at least 12 h before pill intake.