PHARMACOKINETICS AND BIOEQUIVALENCE STUDIES OF TWO NIMESULIDE 100 mg TABLETS: UNIT DOSE, RANDOMIZED-SEQUENCE, TWO-WAY CROSSOVER STUDY IN HEALTHY VOLUNTEERS OF PAKISTANI POPULATION.

ABSTRACT

Single centered crossover, two cycles volunteer study was performed on 12 healthy male volunteers. Both reference and test, immediate release nimesulide formulation was given in a randomized manner with a washout period of 15 days and 5 mL of blood samples were drawn at 0.5, 1, 1.5, 2, 4, 8, 12 and 24 h. Plasma after centrifugation and deproteination, 100 µL of the sample was injected using already validated HPLC method. In plasma LOQ was 0.01 ± 0.012 µg/mL, LOD was 0.001 µg/mL and linearity was observed from 10 to 0.001 pg/mL. Pharmacokinetic parameters including in vivo bioequivalence were studied by using Kinetica 4.4.1. software. The average values of AUC,, was found to be 23.654 ± 0.688 and 23.532 ± 0.662 mg/L x h while C.. values were 6.101 ± 0.403 and 6.072 ± 0.403 pg/mL, respectively. Mean clearance and volume of distribution of reference formulation were 64.062 ± 3.086 mL/h/kg and 9.416 ± 4.767 L, respectively. The disposition rate constant in reference formulation was 0.339 ± 0.598 h' while in immediate release it was 0.467 ± 0.481 h-'. Absorption rate constant and distribution rate constant for reference brand were 1.409 ± 0.251 h- and 1.201 ± 0.283 h' while in immediate release formulation these values were 1.420 ± 0.214 h-' and 1.227 ± 0.263 h', respectively. Bioequivalence results showed 90% confidence of interval for compartmental parameters like Cmax was 99.1 to 100.3%, Tmax. was 98.198 to 99.658% and AUClast, was 99.88 to 100.08% and all were within range.