Study on the in vivo-in vitro Correlation of Cinacalcet Hydrochloride Tablets / 中国药房

ABSTRACT

OBJECTIVE:To investigate the in vitro dissolution behavior and in vivo pharmacokinetics of Cinacalcet hydrochloride tablets, and to evaluate its in vivo-in vitro correlation (IVIVC). METHODS:HPLC method was adopted to determine the accumulative dissolution(Q) of Cinacalcet hydrochloride tablets in 8 kinds of medium [pH 1.2 hydrochloric acid solution,pH 2.0 hydrochloric acid solution,pH 4.5 acetate buffer solution,pH 6.8 phosphate buffer solution,water,artificial gastric fluid(SGF),full belly artificial intestinal fluid(FeSSIF),fasting artificial intestinal fluid(FaSSIF)],and the dissolution curves were drawn. HPLC-MS method was used to determine the blood concentrations of Cinacalcet hydrochloride tablets. A total of 12 healthy male volunteers were selected and given single oral dose of Cinacalcet hydrochloride tablets 75 mg under the state of fasting or satiety(high-fat food). The blood concentration of cinacalcet hydrochlorid was determined before medication(0 h)and 0.5,1,2,3,4,6,8,12,24 h after medication. Average blood concentration-time curves were drawn. The in vivo accumulative absorption percentage (F) of satiety group was calculated by using DAS 3.0 software. Linear regression of F with in vitro Q was carried out to analyze its IVIVC. RESULTS:There was great difference among dissolution curves of Cinacalcet hydrochloride tablets in 8 kinds of dissolution mediums. There were differences of AUC0→t,AUC0→∞ and cmax between fasting group and satiety group,with statistical significance(P＜0.05),showing high-fat food had significant effect on in vivo pharmacokinetics. Correlation coefficient of in vivo F in satiety group with in vitro Q of the tablets in FeSSIF was highest (0.977 9),manifesting good IVIVC (class A). CONCLUSIONS:The in vitro dissolution behavior of Cinacalcet hydrochloride tablets in FeSSIF(paddle method,50 r/min)is well associated with its in vivo pharmacokinetics,which can be used for predicting in vivo dissolution and absorption of the tablets.