title: Effect of absorption rate on pharmacokinetics of ibuprofen in relation to chiral inversion in humans.
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.affiliation: Department of Pharmacy, Heilongjiang Provincial Second Hospital, 159 Diduan Street, Harbin, Heilongjiang 150010, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Ding
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Jiewen
authors.initials: J
authors.lastname: Sun
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Takaki
authors.initials: T
authors.lastname: Toda
authors.forename: Toru
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kishimoto
authors.forename: Wenhui
authors.initials: W
authors.lastname: Lin
authors.forename: Nobuo
authors.initials: N
authors.lastname: Inotsume
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D007052:Ibuprofen