Kinetic study of serum gentamicin concentrations in baboons after single-dose administration
1991
Watson, J.R. | Stoskopf, M.K. | Rozmiarek, H. | Strandberg, J.D.
This study establishes preliminary pharmacokinetic data on the use of gentamicin sulfate administered IM to baboons. Serum concentrations greater than or equal to 12 microgram/ml are generally agreed to cause toxicosis in human beings. On the basis of preliminary test results suggesting that the manufacturer's recommended dosage for dogs of 4.4 mg/kg of body weight caused potentially toxic serum concentrations, a dosage of 3 mg/kg was chosen to conduct a single-dose kinetic study in 6 baboons. Using a single-compartment model, the gentamicin serum half-life for IM administration of 3 mg of gentamicin/kg was 1.58 hours, and serum concentrations remained below the potentially toxic concentrations reported for human beings. We suggest that a dosage of 3 mg/kg is safer than a dosage of 4.4 mg/kg administered IM to baboons. Minimal inhibitory concentrations for 2 Pseudomonas aeruginosa isolates were less than or equal to 1 microgram/ml. On the basis of our measured elimination half-life of 1.58 hours, it is reasonable to suppose that dosing q 24 h will be inadequate to maintain therapeutic serum concentrations. We calculate that serum concentrations will remain at or above our measured minimal inhibitory concentration for P aeruginosa (1 microgram/ml) for 100% of the treatment time if the animal is dosed q 6 h, 78% for dosing q 8 h, and 52% for dosing q 12 h. Therefore, we suggest 3 mg/kg, q 8 h or q 6 h as appropriate dosing schedules for the use of gentamicin sulfate administered IM to baboons.
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