ISSN:
0899-0042
Keywords:
chiral bioinversion
;
pharmacokinetics
;
(+)-(S)-ibuprofen
;
(-)-(R)-ibuprofen
;
rac-ibuprofen
;
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Using a pharmacokinetic model recently proposed to explain ibuprofen disposition in man,1 plasma concentrations of pure ibuprofen enantiomers were simulated following oral administration of (-)-(R)-ibuprofen, (+)-(S)-ibuprofen, or rac-ibuprofen. Simulated and literature values for AUC's were used to compare S/R ratios for different cases of the model and for different methods of calculating the fraction of R bioinverted to S. Numerical simulation using STELLA confirmed previous results for different cases of bioinversion. Simulated S/R AUC ratios, for administration of the racemate, ranged from 4.0 (presystemic bioinversion) to 1.66 (systemic bioinversion). Literature values for S/R AUC ratios averaged 1.53±0.2 for administration of the racemate; therefore, systemic bioinversion was concluded to be representative of ibuprofen disposition. Additional simulations of S/R AUC ratios, for administration of (-)-(R)-ibuprofen only, ranged from 1.5 (presystemic bioinversion) to 0.66 (systemic bioinversion). Literature values for S/R AUC ratios averaged 0.50±0.9 for administration of (-)-(R)-ibuprofen only, which again supported conclusions of systemic bioinversion. Using different equations for estimation of fraction of R inverted to S (FR→S), results based on simulated data were identical; however, FR→S values based on literature data were different. Therefore, assumptions made for different FR→S equations do not appear to be rigorous. Calculations of FR→S, based on literature data, averaged 0.52 overall, indicating bioavailability of (+)-(S)-ibuprofen may be similar for a 150 mg dose of (+)-(S)-ibuprofen compared to a 200 mg dose of racemate.
Additional Material:
1 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/chir.530030507
