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Pharmacokinetics of ketoprofen enantiomers in monkeys following single and multiple oral administration
Author(s) -
Mauleon David,
Mis Ricard,
Ginesta Joan,
Ortega Elvira,
Vilageliu Jaime,
Basi Nuria,
Carganico Germano
Publication year - 1994
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530060705
Subject(s) - pharmacokinetics , chemistry , ketoprofen , oral administration , enantiomer , volume of distribution , high performance liquid chromatography , chromatography , derivatization , pharmacology , half life , stereochemistry , medicine
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.