Disposition kinetics and distribution of demeclocycline in various biological fluids in female goats

Abstract

A pharmacokinetic study of demeclocycline was carried out following intravenous administration at 5 mg/kg body weight in lactating goats. Demeclocycline appeared within 5 min in plasma, interstitial fluid (isf) and urine, while it appeared at 1 h in milk. Peak concentrations of 21.70 +/- 4.06, 2.67 +/- 0.23, 5.65 +/- 0.45 and 82.23 +/- 10.06 micrograms/ml were attained at 5 min and at 6, 8 and 8 h in plasma, isf, milk and urine respectively. A potentially therapeutic concentration of greater than or equal to 0.5 micrograms/ml was maintained from 5 min-36 h, 30 min-30 h, 1-36 h and 5 min-48 h in plasma, isf, milk and urine respectively. The drug was detectable in all the above biological fluids for at least 48 h. A low distribution half life (t1/2 alpha) of 0.44 +/- 0.04 h and a high elimination half life (t1/2 beta) of 19.24 +/- 1.22 h denote rapid distribution but very slow elimination of the drug in goats. A high tissue plasma concentration ratio [K12:(K21-beta)] of 5.12 +/- 0.97 during the elimination phase and a Vdarea of 1.59 +/- 0.18 L/kg indicate uniform distribution of demeclocycline in the tissues and body fluids of goats. The dosage regimen for maintaining minimum plasma concentration (Cp infinity min = MIC) of 0.5, 1.0 and 1.5 micrograms/ml at selected dosage intervals of 12 and 24 h was also calculated.