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Abstract

Enantioselective disposition of 2-arylpropionic acid nonsteroidal anti-inflammatory drugs. III. Fenoprofen disposition.

P J Hayball and P J Meffin
Journal of Pharmacology and Experimental Therapeutics February 1987, 240 (2) 631-636;
P J Hayball
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P J Meffin
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Abstract

The disposition of fenoprofen enantiomers has been studied in nine healthy rabbits. A mean (S.E.M.) of 0.73 (0.07) of R-fenoprofen was inverted to S-fenoprofen and the distribution volumes for bound plus unbound R-fenoprofen and S-fenoprofen were 50.3 (4.5) and 98.5 (5.9) ml/kg, respectively. A model was developed which predicted the area under the S-fenoprofen plasma concentration-time curve after bolus administration of racemic fenoprofen. The mean (S.E.M.) predicted area, 2.1 (0.2) mg X min/ml/kg, was within 94% of the observed area 2.2 (0.2) mg X min/ml/kg. The effect of phenobarbital on the disposition of fenoprofen enantiomers was examined in an additional eight rabbits. During the control study the glucuronidation of R-fenoprofen exceeded the corresponding clearance term for the S-enantiomer by 2.1-fold. The clearances of individual enantiomers to their respective glucuronides increased after phenobarbital pretreatment by a mean 1.6-fold for R- and 2.3-fold for S-fenoprofen. The clearance of S-fenoprofen by processes other than glucuronidation and elimination of unchanged drug in urine was increased by a mean of 2.1-fold after phenobarbital pretreatment but the fractional inversion and the inversion clearance of R- to S-fenoprofen were not affected. These data indicate that on racemic fenoprofen administration the area under the curve for the pharmacologically active S-enantiomer would be reduced by phenobarbital pretreatment.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 240, Issue 2
1 Feb 1987
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Abstract

Enantioselective disposition of 2-arylpropionic acid nonsteroidal anti-inflammatory drugs. III. Fenoprofen disposition.

P J Hayball and P J Meffin
Journal of Pharmacology and Experimental Therapeutics February 1, 1987, 240 (2) 631-636;

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Abstract

Enantioselective disposition of 2-arylpropionic acid nonsteroidal anti-inflammatory drugs. III. Fenoprofen disposition.

P J Hayball and P J Meffin
Journal of Pharmacology and Experimental Therapeutics February 1, 1987, 240 (2) 631-636;
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