A POPULATION PHARMACOKINETIC STUDY OF ALMINOPROFEN PENETRATION INTO SYNOVIAL-FLUID

The pharmacokinetics of alminoprofen in plasma and synovial fluid (SF) at steady state (300 mg t.i.d.) was studied in 45 patients with knee effusion. Plasma and SF samples, one each per patient, were obtained. Six groups were made according to the time of sampling after ingestion of the 13th dose: 1 h (n = 7), 2 h (n = 7), 4 h (n = 7), 6 h (n = 10) , 8 h (n = 6), 12 h (n = 8). A three-compartment model was used to des cribe alminoprofen kinetics in plasma and SF, with two parameterizatio ns, a 'classical' and a 'physiological' one. The non-linear mixed effe ct model approach was used to estimate the mean and variance of the ph armacokinetic parameters. The mean +/- SE of the estimates (coefficien t of variation of interindividual variability as a percentage) were vo lume of distribution, 11.0 +/- 1.711 (12%); elimination rate constant, 0.236 +/- 0.025 h(-1) (18%); absorption rate constant 2.80 +/- 0.31 h (-1) (464%), clearance of influx into SF, 0.29 +/- 0.14 mL min(-1); cl earance of efflux into plasma, 0.56 +/- 0.25 mL min(-1). These two cle arances were not significantly different, which indicates that passive diffusion occurs in both directions. The mean +/- SD alminoprofen con centration versus time curve in plasma and SF at steady state was simu lated and showed that the mean +/- SD maximal concentration in SF was 8.1 +/- 6.3 mg L(-1) and was obtained 4 h after dose administration.