Untitled

Abstract

An open, randomized, six-way crossover study was conducted in 12 healthy males to assess pharmacokinetics and bioinversion of ibuprofen enantiomers. The mean plasma terminal half-life (t1/2) of R(-)ibuprofen was 1.74 hr when intravenously infused as a racemic mixture and was 1.84 hr when intravenously infused alone. The mean t1/2 of S(+)ibuprofen was 1.77 hr when dosed as S(+)ibuprofen. Examination of values of both the absorption and disposition parameters of R(-)ibuprofen revealed that the kinetics of R(-)ibuprofen were not altered by concurrent administration of S(+)ibuprofen. In this study, there was little or no presystemic inversion of R(-)ibuprofen to its S(+)isomer. Also, 69% of the intravenous dose of R(-)ibuprofen was systemically inverted and 57.6% of the oral dose of R(-)ibuprofen lysinate was bioavailable as S(+)ibuprofen. These results indicate that the bioinversion of R(-)ibuprofen administered orally is mainly systemic. Because bioinversion of R(-)ibuprofen is not complete, S(+)ibuprofen produced higher bioavailability of S(+)ibuprofen (92.0%) than either racemic ibuprofen (70.7%) or R(-)ibuprofen (57.6%). However, bioavailability of R(-)ibuprofen (83.6%) when dosed alone was not significantly different from when dosed as racemic mixture (80.7%).

Preparation and characterization of nanoparticles based on dextran–drug conjugates

“…The concentration of the nanoparticle suspension, which is usually 0.1% after preparation, can be increased up to 1% by rotary evaporation of water without changing the particle size and distribution. Concentrations from 0.1% to 1% should be sufficient because the described dextran-drug conjugates possess very high loading efficiencies and similar particle concentrations are used for pharmacokinetic studies and other nanoparticular systems [17,26]. For biological experiments, it is important to note that the nanoparticle suspensions based on dextran esters are stable under standard sterilizing procedures in an autoclave at 121°C and 2 bar for removing germs [6].…”

Moment Analysis of Stereoselective Enterohepatic Circulation and Unidirectional Chiral Inversion of Ketoprofen Enantiomers in Rat

“…2 The disposition properties of ibuprofen and fenoprofen are significantly different between enantiomers, [3][4][5] and these 2-APAs undergo the unidirectional chiral inversion from R-(-)-enantiomers to S-(+)-enantiomers in humans and animals. [6][7][8] It is reported that R-enantiomers are inverted to S-enantiomers exclusively in the rat liver, [9][10][11][12][13] though chiral inversion in the intestine is also suggested. 9,14 Recently, it was found that R-enantiomers have some pharmacological activities (analgesia).…”

Unidirectional Inversion of Ibuprofen in Caco-2 Cells: Developing a Suitable Model for Presystemic Chiral Inversion Study

“…17,18) Therefore, racemic ibuprofen at concentrations of 5, 10, 20, 40 and 80 mg/ml (corresponding to the concentration of R ibuprofen investigated) were coinubated with Caco-2 cells in the same condition as mentioned above to observe the effect of S-enantiomer on the inversion. The results were presented in Fig.…”