Effect of some anti-cancer drugs and combined chemotherapy on the pharmacokinetics of antipyrine in the rat.
The effect of anti-cancer drugs on the metabolic efficiency of the liver was evaluated by means of phenazone (antipyrine) kinetics individually in each rat. Chlormethine (nitrogranulogen, NG), methotrexate (MTX), floxuridine (fluorouracil, 5-fluorouracil, 5-FU), cyclophosphamide (CY, endoxan), and three cytostatics applied jointly (MTX + 5-FU + CY) were administered ip to the rats, while antipyrine was given intravenously. The anti-cancer drugs: NG, MTX, 5-FU, CY and MTX + 5-FU + CY delayed the elimination of antipyrine. Statistically significant prolongation of the half-life, decrease in the elimination rate constant and the clearance of antipyrine have been found in the rats receiving anti-cancer drugs, as compared to the controls. After the administration of MTX, 5-FU, CY and the joint administration of MTX + 5-FU + CY the volume of distribution did not change, while the volume of distribution of antipyrine decreased after the administration of NG. The activity of the investigated enzymes, i.e., alanine aminotransferase (ALAT), aspartic aminotransferase (AspAT), gamma-glutamyltransferase (GGT), alkaline phosphatase (AP), which are the indicators of various liver dysfunctions, did not change after the administration of NG, MTX, 5-FU, CY and MTX + 5-FU + CY. The administered antineoplastic drugs in mono and polytherapy changed the activity of oxidase mixed function responsible for the metabolism of antipyrine. CY administered to rats in polytherapy had less influence on liver metabolic efficiency than in monotherapy.
Skretkowicz
J
J
Department of Pharmacology, Medical Academy, Lódź, Poland.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000983:Antipyrine / Q000493:pharmacokinetics*; D004798:Enzymes / Q000097:blood; D006207:Half-Life; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D004798:Enzymes; D000983:Antipyrine