Assays - Ibuprofen enantiomers
Pharmacokinetics of Dexibuprofen administered as 200 mg and 400 mg film-coated tablets in healthy volunteers
Author: N. Eller, C. J. Kollenz, H. Schiel, C. Kikuta, H.J. Mascher
Publisher: Int. J. Clin. Pharmacol. Ther. 36 (1998), 414-417
The pharmacokinetic properties of 2 film-coated preparations containing 200 mg and 400 mg dexibuprofen were compared in a single-dose, crossover study in 16 healthy, male volunteers. Dexibuprofen was absorbed rapidly (tmax 2.1 - 2.2 hours) reaching the maximum concentrations of 12.4 µg/ml (200 mg), respectively 12.0 µg/ml (400 mg dose adjusted). For the characteristics AUC0-12 and AUC0-∞ arithmetic means of 49.2 µg x h / ml (200 mg) and 48.2 µg x h / ml (400 mg dose adjusted), respectively 50.5 µg x h / ml (200 mg), and 49.2 µg x h / ml (400 mg) were calculated. No relevant differences for the pharmacokinetic characteristics terminal half-life, clearance, volume of distribution, and mean residence time were observed. A linear dose-relationship was shown over the investigated dose range. Mean ratios after dosage adjustment of the test preparation using the “2 one-sided t-test” procedure were calculated. Bioequivalence was assessed for AUC0-12 with a mean ratio of 97.7 % (90 % CI: 92.4 - 103.3 %), for AUC0-∞ with 97.1 % (90 % CI: 91.4 - 103.1), and for Cmax with 97.5 % (90 % CI: 91.7 - 103.8 %). Both dexibuprofen preparations were well tolerated. No changes in haematological and biochemical parameters were detected.
Preliminary Toxicokinetic Study with Different Crystal Forms of S (+)-Ibuprofen (Dexibuprofen) and R,S-Ibuprofen in Rats
Author: S. Walser, R. Hruby, E. Hesse, H. Heinzl, H.J Mascher
Publisher: Arzneimittelforschung 47, 750 - 754, 1997
The aim of the study was to gain information on the plasma concentration-time profiles of both ibuprofen (CAS 15687-21-1) enantiomers in the rat after single oral application of two different crystal forms of S-(+)-ibuprofen (dexibuprofen, CAS 51146-56-6) and racemic ibuprofen in order to optimize blood-sampling times in a subsequent subchronic toxicity study. The application of either commercial racemic ibuprofen or recrystallised S-(+)-ibuprofen (60 mg/kg) to two groups of 4 rats per blood sampling term was carried out in order to define Cmax and tmax and AUC of the plasma concentrations of the ibuprofen enantiomers. The crystals of commercial (manufactured according to an usual manufacturing procedure) and recrystallised S-(+)- and racemic ibuprofen were different in respect to their shape and size. The recrystallised crystal species of S-(+)- and racemic ibuprofen has better galenic (tabletting-) properties and tablets containing the modified S-(+)-ibuprofen species showed favorable clinical results. The toxicokinetic behaviour of the recrystallised species was investigated in comparison to the commercial crystal species because of its slightly but significantly slower dissolution rat in simulated gastric and enteric juice. As the AUC0-24h of S-(+)-ibuprofen and the AUC0-24h of R-(-)-ibuprofen after application of commercial and recrystallised crystal species were not different, the crystal form apparently did not exert an influence on the extent of absorption of S-(+)-ibuprofen and racemic ibuprofen in the rat. The rat has a high inversion capacity and the inversion of R-(-)-ibuprofen after application of commercial and recrystallised racemic ibuprofen was nearly complete in this study. The effects of crystallinity on solubility in simulated media in vitro did not correlate to the findings on the extent of absorption in the rat in vivo.
Comparison of the bioavailability of Dexibuprofen administered alone or as part of racemic Ibuprofen
Author: B. Gabard, G. Nirnberger, H. Schiel, H.J. Mascher, C. Kikuta, J.M. Mayer
Publisher: Eur. J. Clin. Pharmacol., 48 (1995), 505 - 511
Two bioavailability studies of S(+)-Ibuprofen (dexibuprofen) were conducted in healty volunteers to define the relationship between the bioavailibility of the drug after administration of dexibuprofen alone or as part of ibuprofen racemate. Enantionselective plasma drug analysis was used throughout. In the first study the bioavailability of dexibuprofen from a 400 mg tablet formulation was compared with that from 400 mg in aqueous solution. The tablet formulation did not influence the bioavailability of the drug and dexibuprofen was well absorbed from the gastro-intestinal tract. The second study was divided into three identical parts. Bioavailability of dexibuprofen 200, 400 and 600 mg was compared with its bioavailability from ibuprofen racemate 400, 800 and 1200 mg. The second study showed that the mean relative bioavailability of dexibuprofen to ibuprofen racemate was 0.66, thus enabling the estimation of clinically useful dexibuprofen doses from the usual doses of the racemate. The 95 % confidence interval limits did not include 0.5 leading to the conclusion that administering half of the racemate dose would not provide patients with an adequate amount of therapeutically active drug.