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Steady‐state pharmacokinetics of indobufen enantiomers in patients with obliterative atherosclerosis
Author(s) -
Główka F.K.,
Strzelecka D.,
Zapalski S.
Publication year - 2001
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.1036
Subject(s) - enantiomer , pharmacokinetics , chemistry , pharmacology , high performance liquid chromatography , steady state (chemistry) , chromatography , stereochemistry , medicine , organic chemistry
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 (λ = 275 nm) was used for determination of INDB enantiomers in serum of patients. The ratio AUC R :AUC S 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 (t 1/2 ) was significantly shorter for (+)‐S‐INDB (t 1/2 = 4.5 ± 1.2 h as compared to (−)‐R‐INDB (t 1/2 = 7.4 ± 2.4 h). However, no significant differences were observed in the respective V d 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. Chirality 13:308–312, 2001. © 2001 Wiley‐Liss, Inc.