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PHENOBARBITONE INTERACTION WITH ORAL CONTRACEPTIVE STEROIDS IN THE RABBIT AND RAT
Author(s) -
BACK D.J.,
BRECKENRIDGE A.M.,
CRAWFORD FRANCESCA E.,
ORME M.L'E.,
ROWE P.H.
Publication year - 1980
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1980.tb07033.x
Subject(s) - rabbit (cipher) , norethynodrel , lynestrenol , pharmacology , medicine , endocrinology , research methodology , family planning , population , computer science , environmental health , computer security
1 The effect of phenobarbitone on the single dose pharmacokinetics of the synthetic steroids, ethinyloestradiol (EE 2 ) and norethisterone, has been studied in the rabbit and rat. 2 EE 2 is subject to an extensive first pass effect (96%). The plasma clearance of EE 2 approaches total hepatic blood flow. It is suggested that a secondary peak in EE 2 plasma concentration time curves at 5 h is due to enterohepatic recycling. Phenobarbitone had no effect on plasma EE 2 concentrations following intravenous administration and produced a variable decrease after oral administration. 3 In phenobarbitone‐treated rabbits, following intravenous administration of norethisterone there was no significant change in the area under the curve (AUC) compared to controls. In contrast, following oral administration of norethisterone to treated rabbits, the AUC was 20% and the peak plasma concentration 17% of that in controls. 4 The data in rabbits are consistent with drugs which are highly extracted by the liver. 5 In rats, phenobarbitone had no effect on plasma norethisterone concentrations following intravenous or hepatic portal (bolus) administration, but caused a decrease in systemic availability after both infusion into the portal vein (over a period of 5 min) and oral administration. 6 It is concluded that the rate of delivery of norethisterone to the liver is important in determining whether or not enzyme induction will cause an increased first pass effect. 7 Phenobarbitone caused an increase in conjugation of norethisterone in the gastrointestinal tract of rats.