The pharmacokinetics of baclofen derived from intestinal infusion

Abstract

The pharmacokinetics of baclofen, a centrally acting muscle relaxant, have been elucidated in man. The pharmacokinetic disposition was determined form plasma concentration-time data and urinary recovery after the administration of rate-limiting intestinal infusions and an oral bolus dose. Based on comparisons between the plasma concentration-time profiles from the intestinal infusions and the oral bolus doses, relative regression parameter assignments were made. The intestinal absorption of baclofen after intestinal infusion was very rapid, such that baclofen disposition was well characterized by an open two-compartment pharmacokinetic model with zero-order input. Intravenous administration of baclofen was precluded from this study because of the potential for severe adverse reactions. The average distribution phase constant (alpha) was 1.29 hours-1 and the average elimination phase constant (beta) was 0.191 hours-1. Average volume of the central compartment (Vc/F), volume of the body compartment (Varea/F), systemic clearance (CL/F), and renal clearance were 28.8 L, 59.0 L, 180 ml/min, and 103 ml/min, respectively. Pharmacokinetics were dose proportional in the dose range studied. The use of these pharmacokinetic parameters as determined in normal subjects in therapeutic management is particularly relevant, because baclofen is targeted to a patient population subject to renal dysfunction.