Tetracycline antimicrobials are bacteriostatic agents that act by binding to the bacterial 30S ribosomal subunit to inhibit protein synthesis. These agents have broadspectrum activity and have been used for the treatment of various microbial infections including those caused by anaerobic bacteria, Chlamydophila (Chlamydia) spp, and Rickettsia spp. Minocycline is a second-generation antimicrobial of the tetracycline group and has greater lipophilicity and antimicrobial activity than other tetracycline agents.1,2 The excellent lipid solubility of minocycline leads to good distribution in various tissues throughout the body, including penetration of the blood-brain and blood-ocular barriers.3 In dogs, rats, and humans, tissue concentrations of minocycline are generally higher than their serum concentrations.3–5
Minocycline is more active against gram-positive bacteria than gram-negative bacteria.6 Gram-positive bacteria of particular relevance include tetracycline-resistant strains or methicillin-resistant strains of Staphylococcus aureus, and pharmacokineticpharmacodynamic models for activity against S aureus have been reported.2,7 A study5 involving humans revealed minocycline is rapidly and completely absorbed after oral administration and has a prolonged biological half-life of approximately 16 hours. The long half-life allows minocycline to be used effectively to treat infections with administration of 1 or 2 doses/d.
In horses, minocycline may be used when other antimicrobials, such as gentamicin or cephalothin, have failed. This drug is commonly administered at the recommended human dosage (2.2 mg/kg, IV, q 12 h or q 24 h) in horses, but the effect of this dosage has not been evaluated in horses. Tetracyclines are known to cause serious adverse reactions that consist mainly of cardiovascular depression or hypotension in dogs, ruminants, and horses.8–12 For the effective and safe use of antimicrobials, it is important to evaluate their pharmacokinetic and tissue distribution in the target species. Pharmacokinetic data on minocycline are available for dogs,1,8 ruminants,13,14 rabbits,15 and humans.5,16,17 In horses, the pharmacokinetics and tissue distribution of doxycycline, which has a similar structure and bacteriologic properties to minocycline, have been reported18–20 but there is no comparable pharmacokinetic information for minocycline. The purpose of the study reported here was to determine the pharmacokinetics and tissue localization of minocycline in mares after a single IV injection.
Area under the plasma concentration vs time curve from 0 to infinity
Area under the first moment curve from 0 to infinity
Minimal inhibitory concentration
Mean residence time
Reverse-phase high-performance liquid chromatography
Apparent volume of distribution based on area under the curve
Apparent volume of distribution at steady state
Minopen, Sawai Pharmaceutical Co, Yodogawa, Osaka, Japan.
Ravonal, Mitsubishi Tanabe Pharma Co, Osaka, Japan.
Relaxin injection, Kyorin Pharmaceutical Co, Tokyo, Japan.
Domitor, Nippon Zenyaku Kogyo Co, Fukushima, Japan.
Demeclocycline hydrochloride, Sigma-Aldrich Co, St Louis, Mo.
Polytron-aggregate, Kinematica Inc, Littau-Lucerne, Switzerland.
Oasis HLB extraction cartridge, Waters Co, Milford, Mass.
Prominence, Shimadzu Co, Tokyo, Japan.
Nonafluoropentanoic acid, Sigma-Aldrich Co, St Louis, Mo.
COSMOSIL 5C18-MS-2, Nacalai Tesque Inc, Kyoto, Japan.
Minocycline hydrochloride, Sigma-Aldrich Co, St Louis, Mo.
SAAM- II program, University of Washington, Seattle, Wash.
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