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.
In gerbils, ‘minor’ (myoclonic) and ‘major’ (clonictonic) seizures were induced by blowing at the animals with compressed air. The anticonvulsant ED50 of the following drugs was determined after oral administration against both types of seizures: phenytoin, phenobarbital, carbamazepine, sodium valproate, ethosuximide, and diazepam. Valproate, ethosuximide, and diazepam were most potent against ‘minor’ seizures which could not or only partially be suppressed by phenytoin or carbamazepine, respectively. The ‘grand maΓ drugs phenytoin, phenobarbital, and carbamazepine were, on the other hand, more potent against ‘major’ than against ‘minor’ seizures. When phenobarbital was administered for several days, a strong induction of hepatic microsomal enzymes occurred.
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