High-performance Liquid Chromatographic Determination of Stereoselective Disposition of Carprofen in Humans

Stoltenborg, Janet K.; Puglisi, Carl V.; Rubio, F.; Vane, Floie M.

doi:10.1002/jps.2600701107

Cited by 45 publications

(9 citation statements)

References 8 publications

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“…The comparison between enantiomers shows often the difference in these 2 parameters that would be expected for a sole drug according to the variation of the protein binding. For carprofen and flurbiprofen, the more bound S enantiomer presents the higher AVC and tv, (Iwakawa et al 1989;lamali et al 1988a;Spahn et al 1988;Stoltenborg et al 1981;Young et al 1991). For etodolac, the same results are obtained for the R enantiomer (Jamali et al 1988b).…”

Section: Pharmacokinetic Implicationssupporting

confidence: 77%

Protein Binding and Stereoselectivity of Nonsteroidal Anti-Inflammatory Drugs

Lapicque¹,

Muller²,

Payan³

et al. 1993

Clinical Pharmacokinetics

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Stereoselective binding of nonsteroidal anti-inflammatory drugs (NSAIDs) can be studied using various techniques. Thus the results obtained by different investigators may be poorly consistent and even contradictory. NSAIDs are bound stereoselectively to serum albumin to different degrees depending on the drug investigated (ibuprofen, indoprofen, carprofen, etodolac, ketoprofen and flurbiprofen). For other drugs, both enantiomers are bound to a similar extent (pirprofen, fenoprofen). This stereoselectivity could vary with experimental conditions, in particular with protein concentration (ketoprofen, etodolac), leading to individual differences. Finally, the stereoselectivity of protein binding and of pharmacokinetics can be compared: differences in binding between enantiomers can explain their differences in pharmacokinetics, once metabolic properties such as inversion have been taken into account.

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Section: Pharmacokinetic Implicationssupporting

confidence: 77%

Protein Binding and Stereoselectivity of Nonsteroidal Anti-Inflammatory Drugs

Lapicque¹,

Muller²,

Payan³

et al. 1993

Clinical Pharmacokinetics

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“…A pharmacokinetic study on carprofen in three subjects (Stoltenborg et al, 1981) showed a higher V and clearance for the R(-)-enantiomer and no clear difference in terminal half-life between the enantiomers. A pharmacokinetic study on carprofen in three subjects (Stoltenborg et al, 1981) showed a higher V and clearance for the R(-)-enantiomer and no clear difference in terminal half-life between the enantiomers.…”

Section: Discussionmentioning

confidence: 94%

Stereoselective disposition of indoprofen in surgical patients.

Björkman¹

1985

Brit J Clinical Pharma

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The pharmacokinetics of the enantiomers of indoprofen were determined after intravenous administration of the racemate to 10 surgical patients. The mean volume of distribution was 8.97 +/- 2.21 (s.d.) 1 for the pharmacologically active S(+)-enantiomer and 12.60 +/- 4.21 1 for the R(-)-enantiomer (P less than 0.001). The corresponding values for clearance were 32.2 +/- 11.1 ml min-1 and 48.8 +/- 15.5 ml min-1 (P less than 0.001). There was no significant difference in mean terminal half-life between the enantiomers.

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“…In studies on the disposition of R,S-carprofen in the rat, the S(+)-enantiomer was eliminated more slowly than the R( -)-enantiomer, but chiral inversion could not be conclusively demonstrated (Kemmerer et al 1979). In a later study in man, it was found that the stereoselective disposition of carprofen was not as great as in the rat, but the total amount of S(+)-carprofen excreted in urine and faeces, exceeded the R(-)-enantiomer by between 2-5% of the dose (Stoltenborg et al 1981). As yet the administration of individual enantiomers of carprofen to animals or man has not been reported, but available data point to the possibility of its chiral inversion.…”

Section: C Of Ketoprofen S(-)-amethylbenzylamides Has Been Reportementioning

confidence: 94%