Inhibition of antipyrine metabolism by low-dose contraceptives with gestodene and desogestrel.
To examine the effects of the two newest monophasic oral contraceptives on liver microsomal drug metabolism, plasma kinetics and urinary metabolite excretion of antipyrine, a model substrate for liver microsomes, were evaluated. Plasma lipid and lipoprotein levels, and in particular the high-density lipoprotein subfractions, were also monitored in view of their apparent regulation by a P450-dependent system. Ten healthy volunteers were treated with each contraceptive for a period of 3 months in a crossover trial. Both contraceptives significantly reduced antipyrine clearance by 34.6% (gestodene) and 43.3% (desogestrel) by impairing the oxidative metabolism, particularly to the 4-hydroxy and 3-hydroxymethyl metabolites, with little difference between the two associations. In addition, with both a comparable highly significant rise of plasma triglyceride levels, apolipoproteins A-I and A-II and the high-density lipoprotein-3 subfraction was observed. Treatment with these new monophasic contraceptives may reduce the metabolism of concomitantly given drugs undergoing oxidative transformations.
Pazzucconi
F
F
Institute of Pharmacological Sciences, University of Milano, Italy.
Malavasi
B
B
Galli
G
G
Franceschini
G
G
Calabresi
L
L
Sirtori
C R
CR
D000328:Adult; D000983:Antipyrine / Q000378:metabolism* / Q000493:pharmacokinetics; D008076:Cholesterol, HDL / Q000097:blood; D003276:Contraceptives, Oral / Q000008:administration & dosage / Q000494:pharmacology*; D017135:Desogestrel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D009652:Norpregnenes / Q000008:administration & dosage / Q000494:pharmacology*
D008076:Cholesterol, HDL; D003276:Contraceptives, Oral; D008055:Lipids; D008074:Lipoproteins; D009652:Norpregnenes; C033273:Gestodene; D017135:Desogestrel; D000983:Antipyrine