[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.
Drug Safety Research Center, Daiich Pharmaceutical Co., Ltd., Tokyo, Japan.
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Ohno
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Tojo
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Kajimura
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Nomura
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