J. vet.Pharmncol. Therap. 13,415424,1990. Comparative pharmacokinetics of doxycycline in cats and dogs J.-L. RIOND, S. L. VADEN & J. E. RIVIERE Laboratory of Toxicokinetics, Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA Riond, J.-L., Vaden, S.L. & Riviere, J.E. Comparative pharmacokinetics of doxycycline in cats and dogs. J. vet. Phannacol. Tbap. 13. 415-424. The disposition of doxycycline hyclate was studied in six adult mixed-breed female cats and six adult mid-sized female dogs following a single intravenous administration of 5 mg/kg body weight. Doxycycline volume of the central compartment, area volume of distribution, volume of distribution at steady state, and total body clearance were significantly smaller in cats. The differences were attributed to more extensive binding of doxycycline to plasma protein including albumin in cats. ,The significant differences in the volume of distribution and total body clearance were not reflected in elimination half-lives under the conditions of this study (sample size, inhomogeneous population). Doxycycline elimination half-life was 4.56 5 0.68 (SEM) h for cats and 6.99 k 1.09 h for dogs. Dosage regimens recommended in the veterinary literature were evaluated by the computer program PETDR. Dr J. E. Riviere, Laboratory of Toxicokinetus, Department of Ana.tomy, Physiological Sciences, and Radiology, ColItge of Velerinaty Medicine. North Carolinn Stale University, Raleigh, NC 27606, USA. INTRODUCTION Doxycycline is a member of the tetracycline antimicrobial class and has been used orally and intravenously in human medicine for more than 20 years (Aronson, 1980; Cunha et al., 1982; Shaw & Rubin, 1986; Riond & Riviere, 1988). Because it is more lipophilic than methacycline, demeclocycline, chlor- tetracycline, oxytetracycline and tetracycline, doxycycline is characterized by a compara- tively better penetration into tissues which is. reflected by a large volume of distribution despite extensive bindirig to plasma proteins (Schach von Wittenau & Yeary. 1963; Schach von Wittenau 8c Delahunt, 1965; Bana et al., 1975). Lipophilicity is also associated with enhanced in-vitro and in-vivo antimicrobial activity (English, 1966; Rosenblatt et al., 1966). The disposition and antibacterial activity of doxycycline is similar to that of another member of the tetracycline family: minocyc- line (Allen, 1976; Aronson et al., 1980). Wide- spread use of doxycycline in human medicine has confirmed the therapeutic efficacy and safety of the drug (Cunha et al., 1982). Doxycycline has been shown to be efficacious for the treatment of canine ehrlichiosis (Van Heerden & Immelman, 1979). Experiment- ally induced bacterial prostatitis of dogs responded favorably to large doses of doxy- cycline (Baumueller & Madsen. 1977). In contrast to oxytetracycline and tetracycline, doxycycline does not 'accumulate in rats, human beings and dogs with renal failure. This is attributable to passive diffusion of doxycycline into the lumen of the intestine and binding to metallic ions and other mole- cules (Schach von Wittenau & Twomey, 1971; Schach von Wittenau et al., 1972; Whelton et 415