Donovan Joanne M, Kisicki James C, Stiles Mark R, Tracewell William G, Burke Steven K
GelTex Pharmaceuticals, Waltham, MA 02451-1122, USA.
Ann Pharmacother. 2002 Mar;36(3):392-7. doi: 10.1345/aph.1A144.
To assess potential interactions of colesevelam hydrochloride and lovastatin in healthy volunteers when lovastatin alone was administered with dinner, both lovastatin and colesevelam were administered with dinner, and colesevelam was administered with dinner and lovastatin was administered 4 hours later with a snack.
A single-center, open-label, 3-period, crossover drug interaction study was performed with 22 healthy volunteers. Blood samples were collected at specified intervals before and after dosing, and plasma concentrations of lovastatin and lovastatin hydroxyacid were measured using a liquid chromatography/mass spectroscopy/mass spectroscopy method.
Maximal concentration (Cmax), AUC from time 0 to the last time point measured (AUC0-t), and AUC0-infinity values for lovastatin were 102%, 94%, and 104%, and for lovastatin hydroxyacid were 102%, 91%, and 92%, respectively, of control values when colesevelam and lovastatin were coadministered with dinner. Administration of colesevelam with dinner and lovastatin 4 hours later with a snack resulted in a decreased Cmax and AUC0-t for lovastatin (63% and 37%, respectively; p < 0.05) and an increased Cmax and AUC0-t for lovastatin hydroxyacid (61% and 50%, respectively; p < 0.05), both compared with lovastatin alone administered with dinner.
Colesevelam had no significant effect on lovastatin pharmacokinetics when coadministered with lovastatin at dinner. A split-dosing regimen resulted in alterations in pharmacokinetic parameters for lovastatin and lovastatin hydroxyacid that are likely due to known differences in the pharmacokinetics of lovastatin when administered to patients with meals or in a fasting state.
评估盐酸考来维仑与洛伐他汀在健康志愿者中的潜在相互作用，具体情况为单独服用洛伐他汀并与晚餐同服、洛伐他汀和盐酸考来维仑均与晚餐同服，以及盐酸考来维仑与晚餐同服且洛伐他汀在4小时后与零食同服。
对22名健康志愿者进行了一项单中心、开放标签、3期交叉药物相互作用研究。在给药前后的特定时间间隔采集血样，采用液相色谱/质谱/质谱法测定洛伐他汀和洛伐他汀羟酸的血浆浓度。
当盐酸考来维仑和洛伐他汀与晚餐同时服用时，洛伐他汀的最大浓度（Cmax）、从0到最后一个测量时间点的药时曲线下面积（AUC0-t）以及AUC0-无穷大值分别为对照值的102%、94%和104%，洛伐他汀羟酸的相应值分别为102%、91%和92%。与单独晚餐时服用洛伐他汀相比，晚餐时服用盐酸考来维仑且4小时后与零食一起服用洛伐他汀导致洛伐他汀的Cmax和AUC0-t降低（分别为63%和37%；p<0.05），而洛伐他汀羟酸的Cmax和AUC0-t升高（分别为61%和50%；p<0.05）。
晚餐时盐酸考来维仑与洛伐他汀同时服用时，对洛伐他汀的药代动力学没有显著影响。分剂量给药方案导致洛伐他汀和洛伐他汀羟酸的药代动力学参数发生改变，这可能是由于已知的洛伐他汀在餐时或空腹状态下给药时药代动力学的差异所致。
