The Pharmacokinetics And Relative Bioavaliability Of Sulindac In Healthy Chinese Male Volunteers

Sulindac is a nonsteroidal antiinflammatory drug (NSAID) of the indene acetic acid class. Sulindac can be used to treat rheumatoid arthritis, osteoarthritis and ankylosing spondylitis, Other uses include the treatment of acute gouty arthritis and acute painful shoulder. In recent years, Accumulating evidences have indicated that sulindac appears to reduce the risk of colorectal cancer, decrease the incidence of familial adenomatous polyposis. Compared with other traditional nonsteroidal anti-inflammatory drugs, sulindac has less adverse reactions. Sulindac has been on sale in our country. In our study, a new formulation of sulindac (test) was compared to the reference formulation (SHUDANING).OBJECTIVE To compare the relative bioavailability and bioequivalence of 2 sulindac tablet formulations (200mg) in 18 healthy Chinese male volunteers under fasting conditions.METHODS In a randomized two-period, crossover design with 1-week washout period, a single oral dose (200 mg) of sulindac tablets (test) and SHUDANING (reference) was given to 18 healthy male volunteers respectively.Blood samples (5ml) were collected before the dose and at 0.5, 1, 1.5, 2, 2. 5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10 and 12h after administration. Blood was immediately centrifuged to obtain plasma, and the plasma was stored at -20C until assay. Plasma concentrations of sulindac were analyzed by a validated HPLC method. The pharmacokinetic parameters were determined by using non-compartmental model with a statistic analysis of ANOVA and two-one-side t test. Relative bioavaiiability were calculated by the AUC0-t of the two formulations.RESULTS The time to reach the maximal concentration (tmax, h) for the test formulation was identical to that of the reference SUDANING (1. 86). The area under the curve (AUCO t, ng h/mL), the peak concentration (Cmax, ng/ml) and the area under the curve (AUCO- infinity, ng h/mL) of the test and reference formulations were 18. 21 vs. 18.00, 8. 07 vs. 7. 44, 18. 97 vs. 18.61 respectively. Their elimination Tl/2were (6.99 + 0.71) h and (7.02 + 0.51) h respectively. The relative bioavaliability of the test sulindac formulationsis 101. 15% compared with the reference formulations. There was no significant diffenrence between the two products.CONCLUSIONS Bioequivalence between the test and reference formulation can be concluded.The results and new findings of this study were:1. The HPLC of the test is sensitive, reproducible and accurate HPLC method, the disposal course of the samples is easy and suitable for the research of the human bioavaliability.2. The pharmacokinetics parameters of sulindac in Chinese healthy male volunteers were determined, which can provide the basis for the more rational use of sulindac in Chinese.3. Bioequivalence between the test formulations and reference formulations were concluded.