Stereoselective pharmacokinetics of indobufen from tablets and intramuscular injections in man

The influence of administration route (oral or intramuscular (i.m.)) on the pharmacokinetics of total indobufen (INDB) enantiomers was studied in healthy volunteers after a 200 mg dose as a single oral tablet or i.m. injection. Enantiospecific reversed phase (RP) HPLC with UV detection was used for the determination of INDB enantiomers in serum. INDB enantiomers were isolated from serum by solid phase extraction (SPE) procedure using C18 columns. INDB enantiomers were converted to their L-leucinamide diastereoisomers and separated on a C18 HPLC column. INDB from i.m. injections is absorbed faster (tmax = 0.6–0.9 h) than from tablets (tmax = 1.3–1.8 h). The area under curve (AUC) after administration of the tablet was slightly higher than after i.m. injection. The pharmacokinetic behaviour of (+)-S- and (−)-R-INDB after administration of the tablet was different from i.m. injection of racemic INDB. The (+)-S-enantiomer is more rapidly eliminated than its (−)-R-antipode. Statistically significant differences also occurred between enantiomers in AUC, first order elimination rate constant (k), clearance (Cl). The ratio AUCR:AUCS was similar for the tablet (1.57–1.62) and i.m. injection (1.59–1.62). It was concluded that the formulation and extent of ionisation of rac-INDB (acid or sodium salt of INDB) do not significantly influence its stereoselective pharmacokinetics. Chirality 12:38–42, 2000. © 2000 Wiley-Liss, Inc.