Dockens R C, Greene D S, Barbhaiya R H
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Company, Pharmaceutical Research Institute, Princeton, NJ, USA.
Biopharm Drug Dispos. 1996 Mar;17(2):135-43. doi: 10.1002/(SICI)1099-081X(199603)17:2<135::AID-BDD947>3.0.CO;2-K.
The objective of this study was to assess the effect of food on the pharmacokinetics of nefazodone (NEF). A group of 24 healthy adult male volunteers received a single 200 mg dose of NEF under fasting conditions as well as 5 min after a high-fat breakfast. There was a 1 week washout between treatments. Serial blood samples were collected for 48 h after dosing and assayed by a validated HPLC method for NEF and the metabolites hydroxynefazodone (HO-NEF), m-chlorophenylpiperazine (mCPP), and triazoledione (dione). The mean (SD) peak concentration (Cmax) for NEF was not affected by food and was 416 (220) ng mL-1 and 446 (271) ng mL-1 after the fed and fasted treatments, respectively. The median time to reach Cmax (Tmax) was also unaffected by food and was 2 h for both treatments. However, the mean (SD) area under the curve (AUC) was significantly reduced by food from 1815 (1017) ng h mL-1 to 1409 (695) ng h mL-1. Although there was an 18% decrease in NEF AUC when administered with food, food had no effect on Cmax and Tmax values for NEF, HO-NEF, mCPP or dione or AUC values for HO-NEF, mCPP, or dione, indicating that NEF can be administered without regard to meals.
本研究的目的是评估食物对奈法唑酮（NEF）药代动力学的影响。一组24名健康成年男性志愿者在禁食条件下以及高脂早餐后5分钟接受了单次200mg剂量的NEF。两次治疗之间有1周的洗脱期。给药后48小时采集系列血样，并用经过验证的HPLC方法测定NEF及其代谢产物羟基奈法唑酮（HO-NEF）、间氯苯哌嗪（mCPP）和三唑二酮（二酮）。NEF的平均（标准差）峰浓度（Cmax）不受食物影响，进食和禁食治疗后分别为416（220）ng/mL和446（271）ng/mL。达到Cmax的中位时间（Tmax）也不受食物影响，两种治疗均为2小时。然而，食物使曲线下平均（标准差）面积（AUC）显著降低，从1815（1017）ng·h/mL降至1409（695）ng·h/mL。虽然进食时NEF的AUC下降了18%，但食物对NEF、HO-NEF、mCPP或二酮的Cmax和Tmax值以及HO-NEF、mCPP或二酮的AUC值均无影响，这表明NEF给药无需考虑进餐情况。
