Premium
Inhibition of antipyrine metabolism by low‐dose contraceptives with gestodene and desogestrel
Author(s) -
Pazzucconi Franco,
Malavasi Bruno,
Galli Giovanni,
Franceschini Guido,
Calabresi Laura,
Sirtori Cesare R
Publication year - 1991
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1991.29
Subject(s) - desogestrel , gestodene , levonorgestrel , endocrinology , metabolite , medicine , pharmacology , drug metabolism , metabolism , lipoprotein , pharmacokinetics , chemistry , population , cholesterol , family planning , research methodology , environmental health
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 mi‐crosomes, 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 triglycéride 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. Clinical Pharmacology and Therapeutics (1991) 49, 278–284; doi: 10.1038/clpt.1991.29