Pharmacokinetics of minocycline hydrochloride in clinically normal and hypoproteinemic sheep

Eight adult sheep were given 2.2 mg of minocycline hydrochloride/kg of body weight IV before and after blood was collected to induce hypoproteinemia. The blood collection produced a significant (P less than 0.01) reduction in PCV, hemoglobin, and total serum protein values. Pharmacokinetic evaluation of the serum drug concentration vs time data was performed, using a noncompartmental model based on statistical moment theory. Pharmacokinetic values obtained from the sheep with normal serum protein were 5.94 +/- 1.78 ml/kg/min for clearance, 1.32 +/- 0.16 L/kg for the steady-state volume of distribution, and 3.89 +/- 0.80 hours for mean residence time. Significant differences were not found in these values obtained from the sheep when they were hypoproteinemic. The effective half-life, reported as the harmonic mean, increased from 2.57 hours in sheep before blood collection to 2.91 hours in sheep when they were hypoproteinemic. The 2.2 mg of minocycline/kg administered once or twice daily would not be expected to produce adequate serum concentrations for most susceptible microorganisms. Some evidence that minocycline disposition may follow zero-order kinetics is presented.