Influence of endotoxin on the disposition kinetics and dosage regimens of oxytetracycline in calves.
The influence of endotoxin on the disposition kinetics of oxytetracycline (OTC) (10 mg/kg) was investigated in five healthy ruminating male crossbred calves. The serum concentration-time data of OTC before and after endotoxin challenge were best described by a two-compartment open model. Repeated administration of Escherichia coli endotoxin (1 microg/kg, i.v.) at an interval of 12 h up to 48 h produced a clear rise in the body temperature and an increase in the pulse and respiration rates. Endotoxin caused a significant reduction in mean transit time in tissue compartment (MTTT) (P < or = 0.05), mean residence time in the peripheral tissue compartment (MRTT) (P < or = 0.05), mean residence time in the body (MRTB) (P < or = 0.05), elimination half-life (t1/2lambda2) (P < or = 0.05) and distribution space in tissues (VT) (P < or = 0.01) and at steady-state (Vd(ss)) (P < or = 0.01). Endotoxin had no effect on the distribution clearance (ClD), systemic clearance (Cl) and distribution half-life of OTC, while the values of first order rate constant of transfer of drug from tissue to central compartment (K21) and the zero time intercept at terminal phase (C2) were significantly high. The drug dosage regimens to maintain serum OTC concentrations of 0.5, 1, 2, 4, 6 and 8 microg/mL were also determined in febrile and clinically healthy animals.
Kumar
R
R
Department of Pharmacology, College of Veterinary Science and Animal Husbandry Gujarat Agricultural University, Anand Campus, Anand, India. dr_rajiv@vsnl.net
Malik
J K
JK
D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002417:Cattle; D002418:Cattle Diseases / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005334:Fever / Q000378:metabolism / Q000662:veterinary*; D007275:Injections, Intravenous / Q000662:veterinary; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D010118:Oxytetracycline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D008070:Lipopolysaccharides; C044101:endotoxin, Escherichia coli; D010118:Oxytetracycline