Burke S K, Amin N S, Incerti C, Plone M A, Lee J W
GelTex Pharmaceuticals, Inc., 153 Second Avenue, Waltham, MA 02451, USA.
J Clin Pharmacol. 2001 Feb;41(2):199-205. doi: 10.1177/00912700122009881.
Sevelamer hydrochloride (Renagel) is a nonabsorbed phosphate-binding polymer approved for the treatment of hyperphosphatemia in adult hemodialysis patients. The authors studied the potential effect of sevelamer on the pharmacokinetics of two antihypertensive drugs, enalapril (20 mg) and metoprolol (100 mg), commonly used in end-stage renal disease patients. Two studies were conducted. Both were single dose, crossover design with or without a 2.4 g dose of sevelamer in healthy volunteers. Within each study, there was a 7-day washout interval between the two dose administrations. There were 28 volunteers in the enalapril study and 32 in the metoprolol study. The mean plasma concentrations versus time profiles of enalapril, enalaprilat, and metoprolol were not altered by the simultaneous administration of sevelamer. Values for the ratio of ln[AUC(0-infinity)], ln[AUC(0-t)], and ln(Cmax] with and without sevelamer were approximately 100%, and the 90% confidence intervals for the ratios of these parameters with and without sevelamer were within the 80% to 125% range in all cases except for the ln[Cmax] of enalapril, which had an upper confidence bound of 125.4%. The authors conclude that sevelamer does not interfere with the absorption and elimination of enalapril and metoprolol.
盐酸司维拉姆(Renagel)是一种不被吸收的磷结合聚合物,已被批准用于治疗成年血液透析患者的高磷血症。作者研究了司维拉姆对两种常用于终末期肾病患者的降压药物依那普利(20毫克)和美托洛尔(100毫克)药代动力学的潜在影响。进行了两项研究。两项研究均为单剂量、交叉设计,在健康志愿者中分别给予或不给予2.4克司维拉姆。在每项研究中,两次给药之间有7天的洗脱期。依那普利研究中有28名志愿者,美托洛尔研究中有32名志愿者。同时给予司维拉姆并未改变依那普利、依那普利拉和美托洛尔的平均血浆浓度-时间曲线。给予和未给予司维拉姆时ln[AUC(0-∞)]、ln[AUC(0-t)]和ln(Cmax)的比值约为100%,除依那普利的ln(Cmax)外,所有情况下这些参数给予和未给予司维拉姆时比值的90%置信区间均在80%至125%范围内,依那普利ln(Cmax)的置信上限为125.4%。作者得出结论,司维拉姆不会干扰依那普利和美托洛尔的吸收和消除。