Pharmacokinetics of rifampin in adult sheep

Antoinette D. Jernigan From the Departments of Veterinary Physiology and Pharmacology (Jernigan, Sams) and Veterinary Clinical Sciences (St. Jean, Rings, Sams), College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Guy D. St. Jean From the Departments of Veterinary Physiology and Pharmacology (Jernigan, Sams) and Veterinary Clinical Sciences (St. Jean, Rings, Sams), College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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D. Michael Rings From the Departments of Veterinary Physiology and Pharmacology (Jernigan, Sams) and Veterinary Clinical Sciences (St. Jean, Rings, Sams), College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Richard A. Sams From the Departments of Veterinary Physiology and Pharmacology (Jernigan, Sams) and Veterinary Clinical Sciences (St. Jean, Rings, Sams), College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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SUMMARY

Pharmacokinetics and bioavailability of rifampin in adult sheep were investigated by use of high-performance liquid chromatography for determination of serum concentrations. Eight adult ewes were given rifampin po at the rate of 50 mg of rifampin/kg of body weight. Three weeks after the first experiment, the sheep were given rifampin po and iv at the rate of 20 mg/kg in a cross-over design, with 1 week between treatments. Serum obtained over a 36-hour period was analyzed for rifampin and a potential metabolite, 25-desacetyl-rifampin, using reverse-phase chromatography with uv detection at 254 nm. Data were analyzed by compartmental and noncompartmental models. Analysis by the noncompartmental model of rifampin serum concentrations after iv administration yielded a mean ± sd total body clearance of 1.16 ± 0.21 ml/min/kg, apparent volume of distribution at steady state of 0.45 ± 0.06 L/kg, and terminal elimination rate constant of 0.15 ± 0.04 hour−1. The harmonic mean of the elimination half-life was 4.56 hours. Because of incomplete and continuing absorption, bioavailability was extremely variable after oral administration. Desacetylrifampin was not detected. On the basis of pharmacokinetic values, serum concentrations measured in this study, and published minimal inhibitory concentrations, the dosage of 20 mg of rifampin/kg, po, every 24 hours should provide adequate serum concentrations for treatment of rifampin-susceptible bacterial infections in sheep.

SUMMARY

Pharmacokinetics and bioavailability of rifampin in adult sheep were investigated by use of high-performance liquid chromatography for determination of serum concentrations. Eight adult ewes were given rifampin po at the rate of 50 mg of rifampin/kg of body weight. Three weeks after the first experiment, the sheep were given rifampin po and iv at the rate of 20 mg/kg in a cross-over design, with 1 week between treatments. Serum obtained over a 36-hour period was analyzed for rifampin and a potential metabolite, 25-desacetyl-rifampin, using reverse-phase chromatography with uv detection at 254 nm. Data were analyzed by compartmental and noncompartmental models. Analysis by the noncompartmental model of rifampin serum concentrations after iv administration yielded a mean ± sd total body clearance of 1.16 ± 0.21 ml/min/kg, apparent volume of distribution at steady state of 0.45 ± 0.06 L/kg, and terminal elimination rate constant of 0.15 ± 0.04 hour−1. The harmonic mean of the elimination half-life was 4.56 hours. Because of incomplete and continuing absorption, bioavailability was extremely variable after oral administration. Desacetylrifampin was not detected. On the basis of pharmacokinetic values, serum concentrations measured in this study, and published minimal inhibitory concentrations, the dosage of 20 mg of rifampin/kg, po, every 24 hours should provide adequate serum concentrations for treatment of rifampin-susceptible bacterial infections in sheep.

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