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 describe alminoprofen kinetics in plasma and SF, with two parameterizations, a 'classical' and a 'physiological' one. The non-linear mixed effect model approach was used to estimate the mean and variance of the pharmacokinetic parameters. The mean +/- SE of the estimates (coefficient of variation of interindividual variability as a percentage) were volume 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; clearance of efflux into plasma, 0.56 +/- 0.25 mL min-1. These two clearances were not significantly different, which indicates that passive diffusion occurs in both directions. The mean +/- SD alminoprofen concentration versus time curve in plasma and SF at steady state was simulated 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.
Tod
M
M
Département de Pharmacotoxicologie, Hôpital Avicenne, Bobigny, France.
Pobel
C
C
Le Gros
V
V
Louchahi
K
K
Petitjean
O
O
Brion
N
N
Garcia-Mace
J L
JL
D000042:Absorption; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007719:Knee Joint; D008297:Male; D008875:Middle Aged; D011422:Propionates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013582:Synovial Fluid / Q000378:metabolism*; D014018:Tissue Distribution
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011422:Propionates; C027953:alminoprofen