EFFECT OF WATER-DEPRIVATION ON THE DISPOSITION KINETICS OF ENROFLOXACIN IN CAMELS

Concentrations of enrofloxacin equivalent activity were determined (by microbiological assay) in the serum of normal camels and camels at th e end of a 14-day water-deprivation period following single intravenou s (i.v.), intramuscular (i.m.) and subcutaneous (s,c.) administrations at 2.5 mg/kg. Also, normal camels were given an oral drench of the dr ug at 5 mg/kg. Pharmacokinetic variables were determined using compart mental and non-compartmental analytical methods. Camels lost on averag e 12,5 % of body weight at the end of the water-deprivation period. Th e disposition kinetics of i.v, administered drug in normal and water-d eprived camels were very similar. The t(1/2 beta) was 3.0-3.5 h; MRT w as 4.0-4.5 h; V-c was 0.3 L/kg; V-ss was 1.0 L/kg and CIB was 4.0-4.6 ml/min/kg. The effect of water deprivation on the rate of drug absorpt ion and elimination after i.m, administration was inconsistent, and th ere was also a large degree of variability in the normal animals that precluded statistical significance. After s.c, administration, the mea n absorption half-life (t(1/2abs)) in the water-deprived camels was si gnificantly longer than in the normal camels. Systemic availability (F ) was similar in both normal and water-deprived camels after i.m. dosi ng but was significantly greater (P < 0.05) in normal camels (0.92 com pared with 0.65 in water-deprived camels) after s.c. treatment. In nor mal camels, urinary recovery at 12 h after i.v. and s.c. dosing was 25 % and 15%, respectively, and the extent of serum protein binding range d between 1.7% at 1.8 mu g/mL and 24% at 0.33 mu g/mL. The drug was no t detected in serum after oral administration. Serum and milk enroflox acin equivalent activities were determined after i.v. (one camel) and i.m. (one camel) drug administration. Serum drug concentrations were c onsistently higher than in the milk. The AUC(milk)/AUC(serum) ratios w ere 0.27 and 0.39 after i.v. and i.m, drug administration, respectivel y. An i.m. or s.c. treatment regimen of 2.5 mg/kg q. 12 h is suggested for clinical and bacteriological efficacy trials with enrofloxacin in normally hydrated and dehydrated camels.