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  • Title: Enantioselective disposition of 2-arylpropionic acid nonsteroidal anti-inflammatory drugs. IV. Ketoprofen disposition.
    Author: Abas A, Meffin PJ.
    Journal: J Pharmacol Exp Ther; 1987 Feb; 240(2):637-41. PubMed ID: 3806417.
    Abstract:
    The disposition of ketoprofen enantiomers has been studied in 12 rabbits with normal renal function (control) and in 6 of these rabbits with renal dysfunction. In control animals a mean (S.E.M.) of 0.09 (0.01) of R-ketoprofen was inverted to its S-enantiomer. The mean distribution volumes for R- and S-ketoprofen were 114 (7.4) and 294 (76) ml/kg, respectively. The mean clearance of the R-enantiomer from plasma was 292 (40) ml/kg/hr compared to 36 (3.2) ml/kg/hr for the S-enantiomer. This high degree of enantioselectivity was not due to inversion, renal clearance or clearance by glucuronidation, but was the result of an unknown clearance process(es). Comparing the mean parameters of ketoprofen disposition in renal dysfunction with those in the same animals during the control study, the mean fraction of the R-dose inverted increased by 290%, but this effect was not due to decreased clearance of R-ketoprofen renally or by glucuronidation. The distribution volumes of R- and S-ketoprofen were increased by 200 and 183% by renal dysfunction, consistent with an implied decrease in plasma protein binding. The clearances of bound plus unbound R- and S-ketoprofen from plasma remained unaltered by renal dysfunction.
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