Effect of Haemonchus contortus infection on the clearance of antipyrine, sulfobromophthalein, chloramphenicol, and sulfathiazole in lambs.
A study was made to determine the effect of Haemonchus contortus parasitic infection in lambs on the clearance of several IV administered drugs. Clearance of sulfobromophthalein or sulfathiazole from the plasma of lambs was unaffected by infection with H contortus. Clearance of antipyrine was enhanced by the infection, and thiabendazole treatment did not alter this effect. Clearance of chloramphenicol (CAP), administered as the succinate ester (CAPS), was not changed by the infection, but it was increased after treatment with thiabendazole. Changes in the mean body residence time and initial plasma concentration of CAPS and CAP after treatment with thiabendazole indicate that hydrolysis of CAPS to CAP was reduced. High concentrations of CAPS apparently enhanced its own elimination directly rather than via the expected sequence involving hydrolysis, glucuronidation, and excretion of CAP-glucuronide. Enhanced clearance of antipyrine following infection of lambs with H contortus can be explained in at least 2 ways. First, it is possible that the lambs did not have mature amounts of hepatic drug metabolizing enzyme activity as reported by other investigators, which may be explained by breed differences or animal husbandry practices. Second, infection of lambs by H contortus may have triggered an inductive response in hepatic cytochrome P-450-mediated activities, which might result via a generalized enhancement in hepatic protein synthesis associated with the physiologic response to replace plasma proteins and other blood components lost through gastrointestinal hemorrhage caused by the active feeding of adult worms. Other phase-II reactions such as acetylation, glucuronidation, and glutathione-S-transferase apparently were not affected.
Kawalek
J C
JC
Veterinary Pharmacology/Toxicology Branch, FDA, Beltsville, MD 20705.
Fetterer
R H
RH
D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002701:Chloramphenicol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006188:Haemonchiasis / Q000378:metabolism / Q000662:veterinary*; D008297:Male; D008657:Metabolic Clearance Rate; D012756:Sheep; D012757:Sheep Diseases / Q000378:metabolism* / Q000469:parasitology; D000077589:Sulfathiazole; D013432:Sulfathiazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013448:Sulfobromophthalein / Q000008:administration & dosage / Q000493:pharmacokinetics*
D013432:Sulfathiazoles; D013448:Sulfobromophthalein; D002701:Chloramphenicol; D000983:Antipyrine; D000077589:Sulfathiazole