[Retard effect of acemetacin from a commercial preparation--kinetics in humans following single and multiple...

Acemetacin was given to 14 volunteers in a randomized cross-over arrangement as one single administration of 90 mg (1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxyacetic acid) (as Rantudil, Rantudil forte and Rantudil retard) and the courses of blood levels curves compared. Half-life of absorption was considerably higher with the retard formulation (2.01 instead of 0.58 h). The blood level maximum (tmax) was significantly (p less than 0.05) delayed by the retardation, blood levels were lower after 2 h (p less than 0.01), not significantly different 3-4 h after administration and higher (p less than 0.05) than the immediate release form after 6-10 h. AUC's are 5.82 +/- 4.04 (normal) and 6.75 +/- 3.24 (mumol X l-1 X h retarded). The mean residence time was prolonged from 4.1 to 6.3 h, yielding a sustained release quotient of 1.54. After multiple administration (2 retard capsules/d for 8 d) cmax corresponded to the results obtained after single application, maximum levels at 1.24 mumol X l-1 (mean) being somewhat higher than after single application (1.11 mumol X l-1), which is the usual steady-state behavior. Minimum levels in the steady-state (cmin) were 0.24-0.53 mumol X l-1. Bioavailability (AUC's between applications) was not significantly different. No accumulation was found. Levels measured during 8 days of administration of the Rantudil retard formulation corresponded to blood levels from computer simulations. Biological half-life was 4.03 h, which was similar to data obtained with Rantudil (3 X 60 mg/d) in rheumatic patients.