Determination of pharmacokinetic constants after multiple infusions of drugs
The pharmacokinetics of minaxolone, a new steroidal anesthetic agent, were derived after continuous intravenous infusion and bolus administration in the chronically catheterized sheep. There was a linear relationship between the steady-state blood concentration after continuous iv infusion and the infusion rate used, indicating minaxolone pharmacokinetics were linear. Further experimental evidence in support of this finding was the lack of dose dependence in any pharmacokinetic parameter following bolus doses through the clinical range of 12.5--100 mg. Minaxolone was shown to have a high total body clearance between 3 and 4 liters/min and a terminal half-life between 10 and 20 min. Renal excretion of unchanged minaxolone was less than 1%. Organ clearance studies indicated that minaxolone was totally extracted during passage through the liver but negligible extraction occurred during passage through the kidney and lung.