title: [Troubleshooting of bioinequivalence of compound valsartan tablets].
abstract: The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.
authors: Da
authors: D
authors: Shao
authors: Yi-Fan
authors: YF
authors: Zhang
authors: Yan
authors: Y
authors: Zhan
authors: Xiao-Yan
authors: XY
authors: Chen
authors: Da-Fang
authors: DF
authors: Zhong
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D065546:Drug Liberation; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D000068756:Valsartan / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D013607:Tablets; D006852:Hydrochlorothiazide; D000068756:Valsartan