Fasting and postprandial disposition of R(-)- and S(+)-ibuprofen following oral administration of racemic drug in healthy individuals.
The effects of preceding food intake on the plasma concentrations of R(-)-ibuprofen and the pharmacologically active enantiomer S(+)-ibuprofen were investigated in healthy subjects. A single oral dose of 400 mg racemic ibuprofen was administered either fasting or following a standardized meal. As compared to fasting administration postprandial drug intake resulted in a clear reduction of R(-) and S(+)- ibuprofen plasma concentrations mainly during the initial three hours. The ratio of S(+)/R(-)-ibuprofen postprandially was increased for Cmax and AUC o-tmax as well as for AUC o-infinity. These data are compatible with a meal-induced enhancement of chiral inversion of R(-) to S(+)-ibuprofen. The significant reduction of plasma concentrations of ibuprofen mainly during the initial three hours suggests that the analgesic efficacy is diminished when the drug is taken after a meal. This may to a slight extent be compensated for by a small increase of the metabolic inversion of the R(-)-enantiomer into the active S(+)-form of the drug.
Siemon
D
D
Abteilung Klinische Pharmakologie der Medizinischen Klinik und Poliklinik der Universität Heidelberg, Heidelberg, Germany.
de Vries
J X
JX
Stötzer
F
F
Walter-Sack
I
I
Dietl
R
R
D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004435:Eating; D005215:Fasting; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D019518:Postprandial Period; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen