[The effect of ovariectomy in women on metabolism of phenazone].
The studies were aimed to prove the effect of surgical ovariectomy in women with normal estrogen levels on the metabolism of medicaments in the hepatocyte. Phenazone, which has lost its significance as a medicament, was used as a model substance since it is often used as a preparation in the pharmacokinetic investigations. Phenazone levels in sera of women's blood were tested twice. The first test was carried out in the women before the operation which included among other things a surgical ovariectomy. Before the operation, the women manifested normal estrogen levels. The test was repeated 30 days after the operation. Phenazone levels were again tested after oral administration of phenazone in the dose of 18 mg/kg body mass. Before each test, the women were checked twice for the clinical and laboratory parameters of liver functions. Phenazone levels were determined seven times in the blood serum at 3- to 6-hour intervals within 24 hours. The determinations were performed using the Brodie (Brody) method. Average phenazone levels in blood sera were given mathematical analysis in the women before and after surgical ovarlectomy. The two curves were compared to obtain statistically significant differences in most pharmacokinetic parameters. It was shown that sudden drop in estrogen levels due to surgical ovariectomy causes a diminished constant elimination (K), prolongation of half-life (t0.5), an increase in distribution volume (Vd), its reduced derivative (Vd) and increased distribution volume calculated from the area under the curve (VdAUC). It points to the effect of estrogens on the metabolism of medicaments in the liver and indicates a careful dosage of some medicines in chronic use which have a long biological half-life in post-menopausal women and in women following surgical ovariectomy.
Konieczny
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Kliniki Ginekologii IGiP w Poznaniu.
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood*; D000983:Antipyrine / Q000097:blood*; D019540:Area Under Curve; D005260:Female; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008875:Middle Aged; D010052:Ovariectomy; D017698:Postmenopause / Q000378:metabolism; D012016:Reference Values
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000983:Antipyrine