Pharmacokinetics of chloramphenicol in calves during the first weeks of life

Abstract

The pharmacokinetics of chloramphenicol, either administered as the monosuccinate ester or as a veterinary formulation, were studied in calves from the first day of life to the age of 10–12 weeks and compared with the results obtained in adult cattle. (1) After intravenous injection of 0.15 mmol/kg chloramphenicol monosuccinate, the plasma elimination half life of intact ester fell from a value of 33 min on the first day of life to 15 min at the age of 10–12 weeks (value in cows = 14 min). Free chloramphenicol reached maximal plasma concentrations after 2–3 h on the first day of life, but in less than 15 min in cows. The elimination half‐life fell from about 15 h on day 1 to 4.8 h at the age of 10–12 weeks (4.2 h in cows). The bioavailability of the ester was more than 90% on Day 1, but declined to 50–60% from Day 7 on account of rapid renal excretion: 21–28% of the total dose was excreted as intact ester in a 2 h period following injection in calves aged 10–12 weeks. (2) The veterinary formulation of chloramphenicol proved toxic when administered intravenously at a dose of 0.15 mmol/kg, and even a dose of 0.093 mmol/kg was less well tolerated than 0.15 mmol/kg of the monosuccinate ester. (3) The pharmacokinetics of chloramphenicol fitted an open two‐compartment model, the half‐life of the elimination phase corresponded well to the values determined in the experiments with the monosuccinate ester. (4) The intramuscular injection of 0.15 mmol/kg of the ester or 0.093 mmol/kg of chloramphenicol provided ‘therapeutic’ plasma concentrations (≥ 5 μg/ml) within 15–30 min and for about 24 h in calves aged 7 days. (5) Chloramphenicol crossed the placenta when given to cows shortly before a Caesarian section, but equilibrium was not reached within 50–100 min. (6) The binding of chloramphenicol to serum proteins was dependent both on total protein and drug concentrations. It rose from less than 30% on day 1 to about 40% in adult cattle. (7) Recommendations for a dosage regime for chloramphenicol in calves are made on the basis of the pharmacokinetic data.

The pharmacokinetics of thiamphenicol in lactating cows

“…The mean intramuscular bioavailability of about 100% was similar to values reported for various formulations of CAP in cattle (Archimbault et al, 1980;Reiche et al, 1980) and that reported for TAP by Signorini and colleagues (1986). This finding is in agreement with the high lipophilicity of the drug.…”

Pharmacokinetics and distribution in interstitial and pulmonary epithelial lining fluid of danofloxacin in ruminant and preruminant calves

“…At birth, both phase I (primarily oxidation) and phase II (conjugation) metabolic enzymes in the liver may be immature, as well as lack of functional tubular transporters in the kidneys. Maturation of different elimination pathways (including liver and kidney) may impact drug metabolism and clearance and may explain why the impact of age on the reported mean half-lives vary depending on the class of drugs studied (Reiche et al, 1980;Nouws et al, 1983). The increase in glomerular filtration rate (GFR) in neonates during the first few weeks of life is mainly due to an increase in renal blood flow, which would increase the clearance values of drugs eliminated by renal pathways as calves mature (Baroni et al, 2008).…”

Antimicrobial selection and dosage in the treatment of equine bacterial infections

“…The rate at which the metabolic pathways develop varies not only with the species of animal but also with the individual reaction. In foals they appear to reach functional maturity within two weeks after birth, which indicates more rapid development of metabolic pathways than in other domestic animals (Short and Davis 1970;Reiche, Mulling and Frey 1980). The lack of uniformity in development of oxidative reactions reflects the multiplicity of cytochrome P-450 enzymes (Mannering 1985).…”