In vivo release of oxytetracycline from a biodegradable controlled-release gel injected subcutaneously in Japanese quail (Coturnix coturnix japonica) L. A. TELL* Y. SUN   M. NEEDHAM* J. R. JOHNSON   & A. SHUKLA   *Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis;   Department of Pharmaceutical Sciences, College of Pharmacy, Memphis, TN, USA Tell, L. A., Sun, Y., Needham, M., Johnson, J. R., Shukla, A. In vivo release of oxytetracycline from a biodegradable controlled-release gel injected subcuta- neously in Japanese quail (Coturnix coturnix japonica). J. vet. Pharmacol. Therap. 26, 239–245. A long-acting, biodegradable, controlled-release formulation of oxytetracycline (CR-OTC) was evaluated in 18 adult Japanese quail (Coturnix coturnix japonica) following a single subcutaneous (s.c.) injection. Prior to characterizing the release of oxytetracycline (OTC) from the CR-OTC, the pharmacokinetic parameters of intravenously (i.v.) administered OTC were determined. Concentrations of free OTC were measured using a bioassay. The plasma concentration–time profile of OTC after a single i.v. injection at 20 mg/kg was best fit to an open two-compartmental model, with the following pharmaco- kinetic parameters: area under the curve (AUC) ¼ 36.72 mg Æ h/L, terminal elimination half-life ¼ 2.34 h, clearance (Cl) ¼ 0.545 L/kg/h. Plasma [OTC] was >1.0 lg/mL for at least 4 h following i.v. injection. The CR-OTC gel was well tolerated at a dosage of 1500 mg/kg s.c. Plasma [OTC] rose to >1.0 lg/mL within 24 h; it remained >1.0 lg/mL for at least 10 days in all birds sampled at that time point (n ¼ 9) and for at least 18 days in two of nine birds. Using a deconvolution technique, it was determined that approximately 54.8% of the administered OTC was released from the CR-OTC over the 45-day observation period. This long-acting, biodegradable con- trolled-release OTC formulation may have potential for the treatment of chlamydophila infections and other OTC-sensitive bacteria in Japanese quail, however further studies are necessary to determine its safety and clinical application. (Paper received 18 July 2002; accepted for publication 26 February 2003) Lisa A. Tell, Department of Medicine and Epidemiology, Tupper Hall, Room 2108, Davis, CA 95616, USA. E-mail: latell@ucdavis.edu INTRODUCTION Chlamydophila psittaci (formerly known as Chlamydia psittaci; Everett et al., 1999) is a worldwide zoonotic pathogen of poultry and nonpoultry (companion and free-ranging) avian species (Mohan, 1984; Vanrompay et al., 1995, 1997). Tetracyclines are antimicrobial drugs associated with time dependent bacteriostatic effects (Zhanel, 2001), and are the drug class of choice for the treatment of avian chlamydophila infections (Vanrompay et al., 1995). As Chlamydophila spp. are capable of latency and are only susceptible to tetracyclines when actively replicating (Gylstorff, 1987), treatment for 45 days is recommended (Arnstein et al., 1968; Wachendo ¨rfer, 1973). The most common tetracyclines used to treat chlamydophila infections are chlortetracycline (CTC), oxytetracycline (OTC), and doxycycline. These drugs can be administered orally (direct or in feed or drinking water) or parenterally [intramuscular (i.m.) or subcutaneous (s.c.) injection]. Administration in feed or water is convenient for the caregiver, however intake may be limited by palatability and health status resulting in subthera- peutic drug plasma concentrations. In addition, administration of medicated feed requires a diet change resulting in an adjustment period and reduced food intake (Wachendo ¨rfer & Lu ¨ thgen, 1974; Flammer et al., 1989). Tetracycline administration via i.m. or s.c. injection avoids the problem of unreliable intake. This administration route is limited to OTC and doxycycline, and requires patient restraint and handling. If long-acting formulations are used, patient handling can be limited to once every 2–3 days for OTC (Skeeles et al., 1984; Flammer et al., 1990) and once every 4–7 days for doxycycline (Wachendo ¨rfer et al., 1982; Gylstorff et al., 1984; Greth et al., 1993). However, injection site reactions have been reported with s.c. or i.m. administration of a long-acting OTC J. vet. Pharmacol. Therap. 26, 239–245, 2003. ANTIINFECTANTS Ó 2003 Blackwell Publishing Ltd 239