Pharmacokinetics and metabolic inertness of doxycycline in young pigs

Jean-Luc Riond From the Laboratory of Toxicokinetics, Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

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 Méd-Vét, PhD
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J. Edmond Riviere From the Laboratory of Toxicokinetics, Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

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 DVM, PhD

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SUMMARY

The disposition of doxycycline hyclate after iv administration of 20 mg/kg of body weight was studied in 6 pigs. Median elimination half-life, estimated in 4 pigs, was 3.92 hours. Mean (± sem) total body clearance was 1.67 ± 0.18 ml/min/kg, and mean apparent volume of distribution at steady state was 0.53 ± 0.04 L/kg. In 2 pigs, secondary peaks in the logarithmic serum concentration-time profile suggested discontinuous enterohepatic cycling, and precluded using these pigs in the pharmacokinetic analysis. The extent of doxycycline binding to serum protein was 93.1 ± 0.2%. Serum or urine from 3 of the pigs was analyzed by use of photodiode array detection and mass spectrometry of a high-performance liquid chromatographic column effluent. These procedures documented lack of doxycycline biotransformation in pigs. It is concluded that, despite an elimination half-life shorter than that reported in other species, doxycycline may be a valuable antimicrobial drug for use in swine practice, pending the development of appropriate formulations.

SUMMARY

The disposition of doxycycline hyclate after iv administration of 20 mg/kg of body weight was studied in 6 pigs. Median elimination half-life, estimated in 4 pigs, was 3.92 hours. Mean (± sem) total body clearance was 1.67 ± 0.18 ml/min/kg, and mean apparent volume of distribution at steady state was 0.53 ± 0.04 L/kg. In 2 pigs, secondary peaks in the logarithmic serum concentration-time profile suggested discontinuous enterohepatic cycling, and precluded using these pigs in the pharmacokinetic analysis. The extent of doxycycline binding to serum protein was 93.1 ± 0.2%. Serum or urine from 3 of the pigs was analyzed by use of photodiode array detection and mass spectrometry of a high-performance liquid chromatographic column effluent. These procedures documented lack of doxycycline biotransformation in pigs. It is concluded that, despite an elimination half-life shorter than that reported in other species, doxycycline may be a valuable antimicrobial drug for use in swine practice, pending the development of appropriate formulations.

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