Effect of fever on pharmacokinetics and disposition in biological fluids of minocycline in goats

摘要

Effect of fever on distribution, kinetic parameters and dosage regimen of minocycline in goats was studied. Concentrations of minocycline (5 mg.kg(-1), i.v.) in plasma, milk, urine and interstitial fluid (ISF) were estimated in six afebrile and febrile goats by microbiological assay. Fever was induced by i.m. injection of lipopolysccharide of Eschreichia coli @ 0.20 mu g.kg(-1) i.m. which induced an in temperature of 1. 5 - 2.0 degrees F after 1 h of injection which was maintained for 8 h. Three injections of endotoxin were given during the period of study. Minocycline attained its mean peak concentration in milk, urine and interstitial fluid (ISF) earlier in febrile goats (0.75 h) than in afebrile goats (1 h). Kinetic parameters like absorption rate constant (alpha), elimination rate constant (beta), elimination rate constant from central to peripheral compartment (K-12), elimination rate constant from peripheral to central constant (K-21) and elimination rate constant from central compartment (Kel) were higher in febrile goats as compared to afebrile goats. Dosage regimen in goat, particularly in febrile condition was calculated so that it may be a guideline for physicians to treat the animals Loading dose and maintenance doses were dependent on a and hence, for maintaining mean therapeutic level of 0.5 mu g/ml in plasma, a loading dose (D*) of 6.9 mg/kg and maintenance dose (D-0) of 4.7 mg/kg at dosage interval (gamma) of 12 h may be used in afebrile goats whereas higher doses of D* of 7.8 mg/ kg followed by D-0 of 6.1 mg/kg at gamma of 12 h may be administered in febrile goats.