Pharmacokinetics of ibuprofen enantiomers in humans following oral administration of tablets with different absorption rates.
Ibuprofen (IB) is a racemic drug and is administered as such. While activity is due mainly to the S enantiomer, pharmacokinetic interpretations, as well as criteria to assess the bioequivalence of IB formulations, are based on measurements of the total (S + R) drug concentrations. IB enantiomers possess different disposition properties mainly as a result of R-to-S isomeric bioinversion. Inversion is maximal during the absorption phase, suggesting, perhaps, involvement of a presystemic process. This concept was evaluated in healthy subjects by crossover administration of four IB tablets having different absorption rates. The plasma concentrations of the individual isomers were measured using a stereospecific gas chromatographic assay. Differences among the products were insignificant with respect to the extent to the absorption. The S:R concentration ratios rose for 4 to 6 hr and then remained relatively unchanged. This observation was consistent with equal terminal t1/2 values for the enantiomers. There were significant differences between the peak times (Tmax) of the products. The S:R ratios of the concentrations at Tmax of S and AUC also differed; significant positive correlations were found between Tmax and the S:R ratios of Cmax. Thus the extent of R-to-S inversion, and hence the potency of a racemic dose of IB, may be absorption rate dependent.
Jamali
F
F
Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Singh
N N
NN
Pasutto
F M
FM
Russell
A S
AS
Coutts
R T
RT
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D013607:Tablets
D013607:Tablets; D007052:Ibuprofen