Study On Pharmacokinetics And Bioavailability Of Compound Tranilast

AIM: To establish the rapid and sensitive assays for determination of tranilast and salbutamol in human plasma by liquid chromatography-mass spectrometry (LC-MS/MS). Then the method was used to study the pharmacokinetics and the relative bioavailability of compound tranilast in healthy male volunteers, to assess the bioequivalence and to provide scientific evidence for reasonable guideline for clinical application.METHOD: The LC-MS/MS methods with high sensitive and high precision, were developed and validated for Tranilast and Salbutamol assays in plasma sample. The plasma sample were precipitated by organic reagent, and separated on chromatographic column. Detection was carried out by multiple reaction monitoring on a LC-MS/MS system. The analytic methodology was evaluated by detecting the limit of quantization for Tranilast and Salbutamol in plasma, drawn recovery rate, stability, RSD of inter-precision and intra-precision, and selectivity and proved whether it could be used in studying the pharmacokinetics and bioequivalence of Tranilast and Salbutamol.According to a two-period, two-sequence, randomized crossover design, the pharmacokinetics of the 22 healthy male volunteers were studied after each was administrated by a single oral dose of compound tranilast tablet (test drug) and compound tranilast capsule (reference drug), respectively. The concentrations of compound tranilast in plasma samples at different time points were determined by LC-MS/MS and the plasma concentrations-time profiles were obtained. The other pharmacokinetic parameters were calculated by pharmacokinetic statistical software BAPP 2.0. Analysis of Variance (ANOVA), two-one side Student's test and (1-2α)% confidential internal were adopted to statistically evaluate the equivalences.RESULTS: After oral administration with single dose of test drug (T) or reference drug (R) at 80 mg tranilast and 2.4 mg salbutamol, respectively. The Tmax values of tranilast were 3.10±0.70 (mean±SD) and 3.10±0.80 h, respectively. The Cmax values of tranilast were 10023.55±2703.03 and 9292.14±2789.61 ng/mL, respectively. The t1/2 values of tranilast were 9.02±0.74 and 9.10±1.04 h, respectively. The AUC0-t values were 92543.51±23971.12 and 87600.41±24644.40 ng?h/mL and the AUC0-∞values were 94745.33±24414.24 and 89887.12±25409.76 ng?h/mL, respectively. According to AUC0-t, the relative bioavailability of test drug was 107.4±16.8 %.The Tmax values of salbutamol were 2.20±0.80 (mean±SD) and 2.30±0.60 h, respectively. The Cmax values of salbutamol were 5.66±1.81 and 5.84±1.02 ng/mL, respectively. The t1/2 values of salbutamol were 7.49±2.26 and 7.52±2.15 h, respectively. The AUC0-t values were 36.71±7.72 and 35.06±6.40 ng?h/mL and the AUC0-∞values were 37.79±8.03 and 35.91±6.63 ng?h/mL, respectively. According to AUC0-t, the relative bioavailability of test drug was 105.9±18.6 %. Statistical analysis (paired t test) showed no significant difference between test drug and reference drug.CONCLUSION: The pharmacokinetics of compound tranilast test drug and reference drug were similar. Analysis of Variance (ANOVA), two-one side Student's test and (1-2α)% confidential internal were adopted to statistically evaluate the equivalences. Based on the pharmacokinetic and statistical results, we could conclude that the test drug is bioequivalent to the reference drug.