PHARMACOKINETIC ANALYSIS OF MIZOLASTINE IN HEALTHY-YOUNG VOLUNTEERS AFTER SINGLE ORAL AND INTRAVENOUS DOSES - NONCOMPARTMENTAL APPROACH ANDCOMPARTMENTAL MODELING

This paper presents the analysis of the kinetics of a new antihistamin e, mizolastine, in 18 healthy volunteers, from concentrations measured after an intravenous infusion and two different oral administrations: tablet and capsule. Two approaches were used to analyze these data: ( i) a noncompartmental approach implemented in PHARM-NCA; (ii) a compar tmental modeling approach implemented in a new S-PLUS library, NLS2,(5 ) which allows the estimation of variance parameters simultaneously wi th the kinetic parameters. For the compartmental modeling approach, tw o-compartment open models were used. According to the Akaike criterion , the best model describing the kinetics of mizolastine after oral adm inistration was the zero-order absorption model. The kinetic parameter s obtained with PHARM-NCA and NLS2 were similar. The estimated duratio n of absorption was greater for the tablets than for the capsules (wit h means equal to 1.13 hi and 0.84 kr respectively). After an intraveno us infusion, the mean estimated clearance was 4.9 L/hr, the mean lambd a(2)-phase apparent volume of distribution was 89.6 L and the mean ter minal half-life was 12.9 hr.