ISSN:
0899-0042
Keywords:
arylpropionic acid
;
ketoprofen
;
chiral inversion
;
stereoselective pharmacokinetics
;
monkey
;
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Pharmacokinetic studies are reported after single oral administration of 3 mg/kg of stereochemically pure (S)-ketoprofen [(S)-KP] and (R)-ketoprofen [(R)-KP] to three male Cynomolgus monkeys and after repeated administration for 6 months of 3, 15 and 75 mg/kg/day of (S)-KP to both male and female monkeys. A high-performance liquid chromatographic (HPLC) analysis was performed without derivatization of the samples, using a chiral column. The pharmacokinetic parameters for (S)-KP after administration of (S)-KP and for (R)-KP after administration of (R)-KP were, respectively, elimination half-life 2.32 ± 0.36 and 1.64 ± 0.40 h; oral clearance 3.50 ± 0.66 and 7.50 ± 3.20 ml/min/kg; apparent volume of distribution 0.74 ± 0.24 and 1.16 ± 0.76 liter/kg; mean residence time 1.79 ± 0.77 and 1.41 ± 0.65 h; area under the concentration/time curve 14.16 ± 2.93 and 7.31 ± 2.98 μg·h/ml. Forty-nine percent unidirectional bioinversion of (R)-KP to (S)-KP was observed in this species and the pharmacokinetic parameters for the (S)-KP resulting from this inversion were also calculated. In the study of 6-month repeated administration of (S)-KP, linear pharmacokinetic behavior and no evidence of drug accumulation were observed at the three dose levels. © 1994 Wiley-Liss, Inc.
Additional Material:
3 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/chir.530060705
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