Veterinary Archives, Vol. 71 No. 5, 2001.
Original scientific paper
Effects of multiple injections of Escherichia coli endotoxin on the pharmacokinetics and dosage regimens of a long acting formulation of oxytetracycline (OTC-LA) in cross-bred calves.
Rajiv Kumar
; Department of Veterinary Pharmacology and Toxicology, College of Veterinary and Animal Science, Rajasthan Agricultural University, Bikaner, India
Jitendra Kumar Malik
; Division of Veterinary Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly India
Abstract
The effect of induced fever on the serum concentrations and pharmacokinetics of a long-acting formulation of oxytetracycline (OTC-LA) was studied in cross-bred calves. Fever was induced and maintained for 72 h by injecting Escherichia coli endotoxin (1μg/kg, i.v.) repeatedly at an interval of 12 h up to 48 h. In addition to producing a clear rise in temperature, endotoxin resulted in a significant (P< 0.05) increase in heart and respiration rates and other signs of clinical disease in calves. Subsequently, significant alterations were recorded in total leucocyte count (TLC), differential leucocyte count (DLC), blood glucose, blood urea nitrogen (BUN) and serum Zn, Cu, Fe and serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (AKP) concentrations in calves. Fever also produced significant perturbations in serum drug concentrations and reduction in absorption and elimination half-lives (t½ka and t½cl), volume of distribution (Vdss) and time to reach peak concentration (Tmax). Fever had no effect on peak serum drug concentration (Cmax), area under curve (AUC), systemic clearance (ClB) and bioavailability (F) of drug. Calculations revealed that the dosage regimens of OTC-LA required to maintain a minimum serum drug concentration of 1μg/ml for 48 h in febrile calves would be 12.20 per cent (loading) and 21.82 per cent (maintenance) higher than required to produce identical serum concentrations of drug in healthy, afebrile calves.
Keywords
pharmacokinetics; endotoxin; E. coli; fever; oxytetracycline; dosage regimens; calves
Hrčak ID:
89351
URI
Publication date:
17.10.2001.
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