title: Steady-state pharmacokinetics of indobufen enantiomers in patients with obliterative atherosclerosis.
abstract: Steady-state pharmacokinetics of indobufen (INDB) enantiomers administered as racemic INDB (rac-INDB) tablets and bleeding time were studied in patients. Two-hundred mg INDB tablets (Ibustrin) were administered twice daily for 7 days to obliterative atherosclerosis patients. Enantiospecific reversed phase (RP) HPLC with UV detection (lambda = 275 nm) was used for determination of INDB enantiomers in serum of patients. The ratio AUCR:AUCS equalled 1.7 +/- 0.2 as a result of higher (-)-R-enantiomer serum levels. The (+)-S-enantiomer was more rapidly eliminated (oral clearance, Cl = 1.1 +/- 0.3 L/h) than its (-)-R-antipode (Cl = 0.7 +/- 0.2 L/h). Therefore, the mean steady/state levels of (-)/R/enantiomer (13.5 +/- 3.8 mg/L) exceeded those of its (+)-S-enantiomer (7.8 +/- 1.8 mg/L). Furthermore, half-life (t1/2) was significantly shorter for (+)-S-INDB (t1/2 = 4.5 +/- 1.2 h as compared to (-)-R-INDB (t1/2 = 7.4 +/- 2.4 h). However, no significant differences were observed in the respective Vd values. The bleeding time of patients was not significantly extended. The above pharmacokinetic data provide a rationale for potential future replacement of INDB racemic tablets with tablets of its (+)-S-enantiomer.
authors.affiliation: Department of Physical Chemistry, K. Marcinkowski University of Medical Sciences, Poznań, Poland. glowka@eucalyptus.usoms.poznan.pl
authors.forename: F K
authors.initials: FK
authors.lastname: Glówka
authors.forename: D
authors.initials: D
authors.lastname: Strzelecka
authors.forename: S
authors.initials: S
authors.lastname: Zapalski
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001162:Arteriosclerosis Obliterans / Q000097:blood*; D001760:Bleeding Time; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D054833:Isoindoles; D008297:Male; D008875:Middle Aged; D010654:Phenylbutyrates / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D013237:Stereoisomerism
chemical_list: D054833:Isoindoles; D010654:Phenylbutyrates; D010975:Platelet Aggregation Inhibitors; C020371:indobufen