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Effect of absorption rate on pharmacokinetics of ibuprofen in relation to chiral inversion in humans.
J Pharm Pharmacol. 2007 Nov; 59(11):1509-13.JP

Abstract

The effect of absorption rate on the pharmacokinetics of ibuprofen enantiomers was investigated in 12 healthy Han Chinese male volunteers following oral administration of immediate-release (IR) and sustained-release (SR) preparations containing racemic ibuprofen (rac-ibuprofen). The area under the curve of the plasma concentration-time curve (AUC; (mean+/-s.d.) values for rac-ibuprofen were 192.90+/-43.47 for the SR preparation and 195.90+/-31.69 microg h mL(-1) for the IR preparation. AUC values for the enantiomers after administration of the SR formulation were 55.38+/-17.79 and 92.51+/-30.68 microg h mL(-1) for R- and S-ibuprofen, respectively, and were 65.94+/-20.06 and 100.81+/-32.28 microg h mL(-1) for R- and S-ibuprofen after administration of the IR preparation. These values did not differ significantly. C(max) values were significantly decreased with the SR preparation: 25.11+/-5.71, 12.24+/-3.79 and 12.38+/-3.55 microg h mL(-1) for rac-, R-, and S-ibuprofen, respectively, after administration of the SR preparation, vs 46.21+/-8.20, 20.82+/-5.90 and 23.46+/-7.30 microg h mL(-1) for rac-, R-, and S-ibuprofen, respectively, after administration of the IR preparation. Mean residence time was significantly increased: 7.01+/-1.29, 5.52+/-1.25 and 7.04+/-1.30 h for rac-, R-, and S-ibuprofen, respectively, after administration of the SR preparation vs 4.34+/-0.89, 3.43+/-0.64 and 4.51+/-0.79 h for rac-, R-, and S-ibuprofen, respectively, after administration of the IR preparation. AUC values for S-ibuprofen were significantly larger than those for R-ibuprofen in both preparations, indicating unidirectional chiral inversion. The S/R ratio of serum concentrations of enantiomers was 1.78-fold higher at 6 h after administration of the SR preparation compared with the IR preparation (P<0.01). These results indicate that ibuprofen undergoes pre-systemic chiral inversion in parallel with a systemic process and that the clinical effects of rac-ibuprofen in humans depend on the absorption rate.

Authors+Show Affiliations

Department of Pharmacy, Heilongjiang Provincial Second Hospital, 159 Diduan Street, Harbin, Heilongjiang 150010, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

17976261

Citation

Ding, Guohua, et al. "Effect of Absorption Rate On Pharmacokinetics of Ibuprofen in Relation to Chiral Inversion in Humans." The Journal of Pharmacy and Pharmacology, vol. 59, no. 11, 2007, pp. 1509-13.
Ding G, Liu Y, Sun J, et al. Effect of absorption rate on pharmacokinetics of ibuprofen in relation to chiral inversion in humans. J Pharm Pharmacol. 2007;59(11):1509-13.
Ding, G., Liu, Y., Sun, J., Takeuchi, Y., Toda, T., Hayakawa, T., Fukushima, S., Kishimoto, S., Lin, W., & Inotsume, N. (2007). Effect of absorption rate on pharmacokinetics of ibuprofen in relation to chiral inversion in humans. The Journal of Pharmacy and Pharmacology, 59(11), 1509-13.
Ding G, et al. Effect of Absorption Rate On Pharmacokinetics of Ibuprofen in Relation to Chiral Inversion in Humans. J Pharm Pharmacol. 2007;59(11):1509-13. PubMed PMID: 17976261.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of absorption rate on pharmacokinetics of ibuprofen in relation to chiral inversion in humans. AU - Ding,Guohua, AU - Liu,Yang, AU - Sun,Jiewen, AU - Takeuchi,Yuriko, AU - Toda,Takaki, AU - Hayakawa,Toru, AU - Fukushima,Shoji, AU - Kishimoto,Shuichi, AU - Lin,Wenhui, AU - Inotsume,Nobuo, PY - 2007/11/3/pubmed PY - 2008/1/9/medline PY - 2007/11/3/entrez SP - 1509 EP - 13 JF - The Journal of pharmacy and pharmacology JO - J Pharm Pharmacol VL - 59 IS - 11 N2 - The effect of absorption rate on the pharmacokinetics of ibuprofen enantiomers was investigated in 12 healthy Han Chinese male volunteers following oral administration of immediate-release (IR) and sustained-release (SR) preparations containing racemic ibuprofen (rac-ibuprofen). The area under the curve of the plasma concentration-time curve (AUC; (mean+/-s.d.) values for rac-ibuprofen were 192.90+/-43.47 for the SR preparation and 195.90+/-31.69 microg h mL(-1) for the IR preparation. AUC values for the enantiomers after administration of the SR formulation were 55.38+/-17.79 and 92.51+/-30.68 microg h mL(-1) for R- and S-ibuprofen, respectively, and were 65.94+/-20.06 and 100.81+/-32.28 microg h mL(-1) for R- and S-ibuprofen after administration of the IR preparation. These values did not differ significantly. C(max) values were significantly decreased with the SR preparation: 25.11+/-5.71, 12.24+/-3.79 and 12.38+/-3.55 microg h mL(-1) for rac-, R-, and S-ibuprofen, respectively, after administration of the SR preparation, vs 46.21+/-8.20, 20.82+/-5.90 and 23.46+/-7.30 microg h mL(-1) for rac-, R-, and S-ibuprofen, respectively, after administration of the IR preparation. Mean residence time was significantly increased: 7.01+/-1.29, 5.52+/-1.25 and 7.04+/-1.30 h for rac-, R-, and S-ibuprofen, respectively, after administration of the SR preparation vs 4.34+/-0.89, 3.43+/-0.64 and 4.51+/-0.79 h for rac-, R-, and S-ibuprofen, respectively, after administration of the IR preparation. AUC values for S-ibuprofen were significantly larger than those for R-ibuprofen in both preparations, indicating unidirectional chiral inversion. The S/R ratio of serum concentrations of enantiomers was 1.78-fold higher at 6 h after administration of the SR preparation compared with the IR preparation (P<0.01). These results indicate that ibuprofen undergoes pre-systemic chiral inversion in parallel with a systemic process and that the clinical effects of rac-ibuprofen in humans depend on the absorption rate. SN - 0022-3573 UR - https://www.unboundmedicine.com/medline/citation/17976261/Effect_of_absorption_rate_on_pharmacokinetics_of_ibuprofen_in_relation_to_chiral_inversion_in_humans_ L2 - https://doi.org/10.1211/jpp.59.11.0007 DB - PRIME DP - Unbound Medicine ER -