Effect of oral high-dose progestins on the disposition of antipyrine, digitoxin, and warfarin in patients with advanced breast cancer.
The influence of two progestins, medroxyprogesterone acetate (MPA) and megestrol acetate (MA), given orally in high doses, on the pharmacokinetics of antipyrine, digitoxin, and warfarin were studied in patients with advanced breast cancer. Antipyrine and warfarin were given as a single test dose before and after 5 weeks of progestin treatment. The pharmacokinetics of digitoxin was investigated at steady state in patients receiving this drug therapeutically before and during treatment with progestins. Small changes in clearance rates for antipyrine, warfarin, and digitoxin were found. A minor decrease observed in warfarin clearance however may be of clinical importance. Half-lives decreased by 13% for antipyrine and increased by 71% for warfarin. High-dose progestins given orally do not seem to have a major influence on drug metabolism, probably reflecting a minor effect on drug and steroid-metabolizing microsomal mono-oxygenases in the liver.
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000983:Antipyrine / Q000097:blood / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004074:Digitoxin / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D017258:Medroxyprogesterone Acetate; D008535:Megestrol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D019290:Megestrol Acetate; D008875:Middle Aged; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014859:Warfarin / Q000097:blood / Q000378:metabolism*
D045167:Progesterone Congeners; D014859:Warfarin; D017258:Medroxyprogesterone Acetate; D004074:Digitoxin; D008535:Megestrol; D008525:Medroxyprogesterone; D000983:Antipyrine; D019290:Megestrol Acetate