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Evidence of absorption rate dependency of ibuprofen inversion in the rat.
Chirality. 1994; 6(5):435-9.C

Abstract

Ibuprofen (IB) is a chiral 2-arylpropionic acid derivative used as a nonsteroidal antiinflammatory drug (NSAID). It undergoes substantial R to S chiral inversion in humans and rats. In addition to systemic inversion, presystemic chiral inversion has been suggested for IB in humans but only after administration of formulations with slow absorption rates. In search for a suitable animal model, the absorption rate dependency of the extent of inversion was examined in male Sprague-Dawley rats given 20 mg/kg of racemic IB in aqueous solution (Tmax, 0.6 h), suspension (Tmax, 1 h) or as sustained release granules (Tmax, 2.3 h). In addition, (R)-IB (5 mg/liter) was incubated in the presence of everted rat gut segments in an organ bath at 37 degrees. After sustained release granules, the S:R AUC ratios (7.3 +/- 1.5) were significantly higher than suspension (3.6 +/- 1.1) and solution (3.5 +/- 0.2). Accordingly, AUCS and AUCR, as percent of the total AUC (S+R), significantly increased and decreased, respectively, after administration of the sustained released granules as compared with the solution and suspension. A significant positive linear correlation was found between the S:R AUC ratios and the corresponding Tmax for (R)-IB (r = 0.82). In vitro, (R)-IB was inverted by everted jejunum (12.2 +/- 1.6%), ileum (14.2 +/- 2.0%), and colon (4.4 +/- 0.6%) segments. IB was also glucuronidated in the presence of the intestinal segments. Therefore, similar to earlier observations made in humans, in the rat, the S:R AUC ratio was positively and significantly correlated with the absorption rate from the dosage form.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8068501

Citation

Sattari, S, and F Jamali. "Evidence of Absorption Rate Dependency of Ibuprofen Inversion in the Rat." Chirality, vol. 6, no. 5, 1994, pp. 435-9.
Sattari S, Jamali F. Evidence of absorption rate dependency of ibuprofen inversion in the rat. Chirality. 1994;6(5):435-9.
Sattari, S., & Jamali, F. (1994). Evidence of absorption rate dependency of ibuprofen inversion in the rat. Chirality, 6(5), 435-9.
Sattari S, Jamali F. Evidence of Absorption Rate Dependency of Ibuprofen Inversion in the Rat. Chirality. 1994;6(5):435-9. PubMed PMID: 8068501.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence of absorption rate dependency of ibuprofen inversion in the rat. AU - Sattari,S, AU - Jamali,F, PY - 1994/1/1/pubmed PY - 1994/1/1/medline PY - 1994/1/1/entrez SP - 435 EP - 9 JF - Chirality JO - Chirality VL - 6 IS - 5 N2 - Ibuprofen (IB) is a chiral 2-arylpropionic acid derivative used as a nonsteroidal antiinflammatory drug (NSAID). It undergoes substantial R to S chiral inversion in humans and rats. In addition to systemic inversion, presystemic chiral inversion has been suggested for IB in humans but only after administration of formulations with slow absorption rates. In search for a suitable animal model, the absorption rate dependency of the extent of inversion was examined in male Sprague-Dawley rats given 20 mg/kg of racemic IB in aqueous solution (Tmax, 0.6 h), suspension (Tmax, 1 h) or as sustained release granules (Tmax, 2.3 h). In addition, (R)-IB (5 mg/liter) was incubated in the presence of everted rat gut segments in an organ bath at 37 degrees. After sustained release granules, the S:R AUC ratios (7.3 +/- 1.5) were significantly higher than suspension (3.6 +/- 1.1) and solution (3.5 +/- 0.2). Accordingly, AUCS and AUCR, as percent of the total AUC (S+R), significantly increased and decreased, respectively, after administration of the sustained released granules as compared with the solution and suspension. A significant positive linear correlation was found between the S:R AUC ratios and the corresponding Tmax for (R)-IB (r = 0.82). In vitro, (R)-IB was inverted by everted jejunum (12.2 +/- 1.6%), ileum (14.2 +/- 2.0%), and colon (4.4 +/- 0.6%) segments. IB was also glucuronidated in the presence of the intestinal segments. Therefore, similar to earlier observations made in humans, in the rat, the S:R AUC ratio was positively and significantly correlated with the absorption rate from the dosage form.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0899-0042 UR - https://www.unboundmedicine.com/medline/citation/8068501/Evidence_of_absorption_rate_dependency_of_ibuprofen_inversion_in_the_rat_ L2 - https://doi.org/10.1002/chir.530060512 DB - PRIME DP - Unbound Medicine ER -