Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

The pharmacokinetics (PK) of ordinary tablets and sustained release capsules of diltiazem hydrochloride in human clinical trials had been studied. The PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules, a new dosage form, has not been reported, although it is very important to clinical use. In this paper, we investigated the PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules and the food influence in Chinese healthy volunteers. The PK parameters indicated that the diltiazem hydrochloride delay-onset sustained-release pellet capsules appeared marked characteristics of delayed and controlled release. An opened-label, randomized and parallel clinical trial was conducted in 36 Chinese healthy volunteers with single oral dose (90 mg, 180 mg or 270 mg) and a multiple oral dose (90 mg d-1×6 d) administration. The effect of food on the PK of one single oral dose (360 mg) was investigated in 24 healthy Chinese volunteers. Plasma diltiazem concentration was determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and the main pharmacokinetic parameters were analyzed by PKSolver (Ver 2.0). All clinical studies were conducted in the Clinical Pharmacological Center (No. JDX1999064) of Xiangya Hospital Affiliated Central South University, China. The PK parameters suggested that the new formulation had marked characteristics of delayed and controlled release of diltiazem, and food intake did not alter significantly diltiazem pharmacokinetic parameters. Embora a farmacocinética (PK) do cloridrato de diltiazem nas formas de comprimidos de libera o imediata e cápsulas de libera o modificada em ensaios clínicos já tenha sido relatada, a pesquisa da PK do cloridrato de diltiazem na forma de cápsulas com peletes de libera o retardada e sustentada ainda é muito importante. Neste trabalho, propusemos avaliar a farmacocinética do cloridrato de diltiazem administrado através desta nova forma farmacêutica em voluntários chineses sadios, assim como a influência da ingest o de alimentos neste perfil farmacocinético. Foi realizado um ensaio clínico aberto, randomizado e paralelo em 36 voluntários, que receberam dose oral única de 90 mg, 180 mg ou 270 mg e dose múltiplas (90 mg/d × 6 d) pela mesma via de administra o. Para avaliar o efeito da ingest o de alimentos sobre a PK do diltiazem foi realizada a administra o de dose única (360 mg) em 24 voluntários chineses sadios. A concentra o plasmática do diltiazem foi determinada por Cromatografia Liquida de Alta Eficiência em fase reversa (CLAE-FR) e os princi