title: Pharmacokinetics of ketoprofen enantiomers in monkeys following single and multiple oral administration.
abstract: 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 micrograms.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.
authors.affiliation: Research and Development Department, Laboratorios Menarini, Badalona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Mauleon
authors.forename: R
authors.initials: R
authors.lastname: Mis
authors.forename: J
authors.initials: J
authors.lastname: Ginesta
authors.forename: E
authors.initials: E
authors.lastname: Ortega
authors.forename: J
authors.initials: J
authors.lastname: Vilageliu
authors.forename: N
authors.initials: N
authors.lastname: Basi
authors.forename: G
authors.initials: G
authors.lastname: Carganico
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D007660:Ketoprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008252:Macaca fascicularis; D008297:Male; D012737:Sex Factors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D007660:Ketoprofen