[Increased serum alkaline phosphatase induced by DT-5061, an oral contraceptive, in rats].
DT-5061, a steroid oral contraceptive which contains norethisterone (NET) and ethinyl estradiol (EE) in a ratio of 100:7, was administered orally to rats for 14 days in order to investigate a possible origin of the increased serum alkaline phosphatase (ALP). Increased serum total ALP was noted in rats receiving DT-5061 at 5.35 mg/kg/day or EE at 0.35 mg/kg/day. Electrophoresis of serum ALP revealed that both liver and bone-type ALP isozymes were increased in the DT-5061 5.35 mg/kg and EE 0.35 mg/kg groups, and the ratio of increase in the liver-type was greater than that in the bone-type although the increase in concentration of the bone-type was greater as compared to the liver-type. ALP level in the liver was elevated together with an increase in liver weight, consistently with the increased serum liver-type isozyme. However, neither histological changes indicative of cholestasis nor increase in serum leucine aminopeptidase, bilirubin, GOT or GPT were seen. No changes were observed in bone ALP activity; hence inconsistent with the increased serum bone-type isozyme. From these results, it is considered that the increased serum ALP induced by this drug was due to the increased liver-type isozyme induced in the liver and to the increased bone-type isozyme, and among the ingredients of this oral contraceptive, EE was mainly involved in the increased serum ALP induced by this drug.
Ohno
H
H
Drug Safety Research Center, Daiich Pharmaceutical Co., Ltd., Tokyo, Japan.
Tojo
H
H
Kajimura
T
T
Nomura
M
M
D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000097:blood*; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000201:enzymology; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000633:toxicity*; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage / Q000633:toxicity*; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007527:Isoenzymes / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009640:Norethindrone / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D004338:Drug Combinations; D007527:Isoenzymes; C020416:norethindrone acetate, ethinyl estradiol, ferrous fumarate drug combination; D004997:Ethinyl Estradiol; D000469:Alkaline Phosphatase; D009640:Norethindrone