Effect of age on the pharmacokinetics of indobufen.
Eighteen patients of both sexes, aging between 54 and 81 years entered a study on the effects of age on the disposition kinetics of indobufen, a potent inhibitor of platelet aggregation. Plasma levels and urinary excretion of the drug were assayed by HPLC after a single oral dose (200 mg) and after the last dose of a repeated oral schedule (200 mg b.i.d. for 5 days). At steady-state, indobufen plasma levels were about double those after the single dose; plasma level profiles were similar. No significant differences were detected between single dose and steady-state as regards pharmacokinetic parameters of the drug which, at steady-state, were (mean +/- SD, n = 16): Cmax = 32.6 +/- 9.3 micrograms/ml, t 1/2 beta = 12.8 +/- 4.4 h, Pl.Cl. = 14.9 +/- 6.1 ml/min, Vd beta = 223 +/- 63 ml/kg. Evidence of reduced efficiency and rate of indobufen elimination was found in elderly patients compared to young healthy subjects. This is probably because of the age-related decrease in renal function. In the patients of the present study, average Cr.Cl. was about 60 ml/min, corresponding to 50-60% of the normal values in young subjects. A statistically significant correlation was found in patients between drug plasma clearance and Cr.Cl. in agreement with the findings of a previous study on the effects of renal insufficiency on indobufen kinetics. The same dose reduction of indobufen as previously suggested for patients with mild to moderate renal insufficiency should, therefore, be adopted in elderly patients.
D000284:Administration, Oral; D000367:Age Factors; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D054833:Isoindoles; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010654:Phenylbutyrates / Q000097:blood* / Q000494:pharmacology / Q000652:urine; D010974:Platelet Aggregation / Q000187:drug effects; D013997:Time Factors
D054833:Isoindoles; D010654:Phenylbutyrates; C020371:indobufen