ASPECTS OF THE PHARMACOKINETICS OF DOXYCYCLINE GIVEN TO HEALTHY AND PNEUMONIC EAST-AFRICAN DWARF GOATS BY INTRAMUSCULAR INJECTION

The effect of experimentally induced Pasteurella haemolytica pneumonia on the pharmacokinetics of doxycycline (Doxycen Retard) administered intramuscularly was studied in seven East African dwarf goats. The stu dy was conducted in two consecutive phases, separated by a washout per iod of four weeks. The experimental infection, induced by intratrachea l administration of 5 ml of 10(7) to 10(9) cfu/ml of Pasteurella haemo lytica, produced a temperature rise, depression and laboured breathing within 6-12 days after inoculation. The concentrations of doxycycline in the serum were determined by a quantitative microbiological assay using an agar-gel diffusion method employing Bacillus cereus var mycoi des (ATCC 11778) as the test organism, with a level of detectability o f approximately 0.05 mu g/ml. The concentration-time curve of doxycycl ine in the serum after intramuscular injection of 20 mg/kg bodyweight of the long-acting formulation before and after experimental infection was adequately described by a one-compartment open model. The maximum serum concentrations (C-max) of doxycycline were lower in pneumonic g oats than in healthy goats (3.87 +/- 0.52 and 5.56 +/- 0.213 mu g/ml, respectively), suggesting an increased distribution volume in the peri pheral compartment. The mean +/- SEM absorption rate (k(a) before infe ction (1.13 +/- 0.02 h(-1)) was smaller than that after infection (8.2 3 +/- 3.81 h(-1)), but the difference was not significant. The apparen t elimination half-life (t(1/2 beta)) (24.51 +/- 0.02 h) after infecti on was significantly increased (p < 0.05), while the corresponding rat e constant (beta) was decreased (p < 0.01). The absorption half-life ( t(1/2 alpha) (0.137 +/- 0.03 h) was significantly decreased (p < 0.01) after infection. The distribution volume (V-d(beta)) was significantl y increased after infection (p < 0.05). It is concluded that, although experimental infection had an effect on the disposition kinetics of d oxycycline, this was not sufficiently pronounced to require alteration of the dosage during disease.