Kinetic study of serum gentamicin concentrations in baboons after single-dose administration

Julie Ralph Watson From the Division of Comparative Medicine, Johns Hopkins School of Medicine, 720 Rutland Ave, Baltimore, MD 21205 (Watson, Stoskopf, Strandberg) and University Laboratory Animal Resources, University of Pennsylvania, 100 Blockley Hall, Philadelphia, PA 19104-6021 (Rozmiarek).

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Michael K. Stoskopf From the Division of Comparative Medicine, Johns Hopkins School of Medicine, 720 Rutland Ave, Baltimore, MD 21205 (Watson, Stoskopf, Strandberg) and University Laboratory Animal Resources, University of Pennsylvania, 100 Blockley Hall, Philadelphia, PA 19104-6021 (Rozmiarek).

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Harry Rozmiarek From the Division of Comparative Medicine, Johns Hopkins School of Medicine, 720 Rutland Ave, Baltimore, MD 21205 (Watson, Stoskopf, Strandberg) and University Laboratory Animal Resources, University of Pennsylvania, 100 Blockley Hall, Philadelphia, PA 19104-6021 (Rozmiarek).

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John D. Strandberg From the Division of Comparative Medicine, Johns Hopkins School of Medicine, 720 Rutland Ave, Baltimore, MD 21205 (Watson, Stoskopf, Strandberg) and University Laboratory Animal Resources, University of Pennsylvania, 100 Blockley Hall, Philadelphia, PA 19104-6021 (Rozmiarek).

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Summary

This study establishes preliminary pharmacokinetic data on the use of gentamicin sulfate administered im to baboons. Serum concentrations ≥ 12 μg/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 ≤ 1 μg/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 μg/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.

Summary

This study establishes preliminary pharmacokinetic data on the use of gentamicin sulfate administered im to baboons. Serum concentrations ≥ 12 μg/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 ≤ 1 μg/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 μg/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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