Comparative bioavailability and pharmacokinetics of Dolotren retard and Dolotren

RESUMEN

A randomized crossover study was designed in order to evaluate the bioequivalence of a sustained-release preparation (DR) of diclofenac sodium (Dolotrén RETARD) with respect to an enteric coated (D) tablet (Dolotren).

For this purpose the bioavailability of both formulations, orally administered in single and multiple doses, was determined. Nine healthy volunteers were included in this study, receiving 100 mg of D and 100 mg of DR, firstly in single dose and then for 15 days b.i.d. for D group and once a day for DR group. For the analytical determination of diclofenac, blood samples at established time intervals, the day of the single dose and the 3rd, 7th and 15th day of multiple dose administration, were taken. The following kinetic parameters were determined: Cmac, tmax, alpha and beta, clearance, ka, area under the curve and absolute and relative bioavailability.

When administered both endovenous and orally, the great interindividual variability in the kinetic characteristics of diclofenac sodium is evidenced. The lag time (tlag) for DR is 0.4 h, shorter than for D (2.2 h), which indicates a faster absorption in the upper sections of the gastrointestinal tract. Also tmax was shorter for Dr (1.9 h) than for D (4.3 h). Cmax obtained with D was higher tan with DR. The diclofenac sodium elimination process from plasma is significantly slower with DR than with D (t1/2 beta = 18.1 h and 2.5 h, respectively). In consequence, quantifiable plasmatic levels are maintained for at least 24 hours after administration of DR, but not of D. Absolute bioavailability of both preparations is about 80%, with great interindividual variations. Significant differences between the two preparations could not be demonstrated. Relative bioavailability between DR and D was 91.5%. None of the preparations when administered in repeated doses, D every 12 hours and DR every 24 hours, produced accumulation, neither their pharmacokinetic characteristics changed.

Clinical and biological tolerance of both preparations were excellent, at doses used and for the period of time studied. Dolotren Retard is absorbed orally faster than Dolotren and maintains plasmatic levels longer, which allows it to be administered once a day, with a lesser incidence of undesirable effects related to Cmax.

CITA DEL ARTÍCULO  Rev Med Univ Navarra. 1992 Jan-Mar;37(1):7-16