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Pharmacokinetics and tissue distribution of minocycline hydrochloride in horses

Shun-ichi Nagata DVM, PhD1, Shozo Yamashita PhD2, Masahiko Kurosawa DVM, PhD3, Masao Kuwajima DVM4, Seiji Hobo DVM, PhD5, Yoshinari Katayama DVM, PhD6, and Toru Anzai DVM, PhD7
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  • 1 Analytical Chemistry Section, Laboratory of Racing Chemistry, 1731–2 Tsurutamachi, Utsunomiya, Tochigi 320–0851, Japan.
  • | 2 Analytical Chemistry Section, Laboratory of Racing Chemistry, 1731–2 Tsurutamachi, Utsunomiya, Tochigi 320–0851, Japan.
  • | 3 Analytical Chemistry Section, Laboratory of Racing Chemistry, 1731–2 Tsurutamachi, Utsunomiya, Tochigi 320–0851, Japan.
  • | 4 Analytical Chemistry Section, Laboratory of Racing Chemistry, 1731–2 Tsurutamachi, Utsunomiya, Tochigi 320–0851, Japan.
  • | 5 Epizootic Research Center, Equine Research Institute, Japan Racing Association, 1400–4 Shiba, Shimotsuke, Tochigi, 329–0412, Japan.
  • | 6 Epizootic Research Center, Equine Research Institute, Japan Racing Association, 1400–4 Shiba, Shimotsuke, Tochigi, 329–0412, Japan.
  • | 7 Epizootic Research Center, Equine Research Institute, Japan Racing Association, 1400–4 Shiba, Shimotsuke, Tochigi, 329–0412, Japan.

Abstract

Objective—To determine the pharmacokinetics and tissue distribution of minocycline in horses.

Animals—5 healthy Thoroughbred mares for the pharmacokinetic experiment and 6 healthy Thoroughbred mares for the tissue distribution experiment.

Procedures—Each mare was given 2.2 mg of minocycline hydrochloride/kg, IV. Blood samples were collected once before minocycline administration (0 hours) and 10 times within 48 hours after administration in the pharmacokinetics study, and 24 tissue samples were obtained at 0.5 and 3 hours in the distribution study.

Results—No adverse effects were observed in any of the mares after minocycline administration. The mean ± SD elimination half-life was 7.70 ± 1.91 hours. The total body clearance was 0.16 ± 0.04 L/h/kg, and the volume of distribution at steady state was 1.53 ± 0.09 L/kg. The percentage of plasma protein binding was 68.1 ± 2.6%. Plasma concentration of free minocycline was 0.12 μg/mL at 12 hours. Minocycline was not detected in brain tissue, CSF or aqueous humor at 0.5 hours; however, it was found in all tissues, except in the aqueous humor, at 3 hours.

Conclusions and Clinical Relevance—Clearance of minocycline in healthy mares was greater than that reported for humans. For effective treatment of infections with common equine pathogens, it will be necessary to administer minocycline at a dosage of 2.2 mg/kg, IV, every 12 hours. This drug could be useful for infections in many tissues, including the CNS. The pharmacokinetic and tissue distribution data should aid in the appropriate use of minocycline in horses. (Am J Vet Res 2010;71:1062–1066)

Contributor Notes

Supported by the Japan Racing Association.

Address correspondence to Dr. Nagata (s-nagata@lrc.or.jp).