Effects of concomitant therapy with diltiazem on the lipid responses to simvastatin in Chinese subjects.
Diltiazem increases systemic exposure to simvastatin via inhibition of CYP3A. This study assessed the impact of this interaction on the lipid-lowering effects of simvastatin. Chinese patients with hypercholesterolemia were randomized to receive simvastatin 20 mg daily alone or together with diltiazem 60 mg 3 times daily for 4 weeks with a washout period of 4 weeks in an open-label, crossover study. Blood pressure, fasting serum lipid profile, and safety tests were determined at baseline and after each treatment period. Trough serum diltiazem was measured at the end of the 4-week combination treatment. In the 30 patients who completed the study, simvastatin treatment significantly reduced low-density lipoprotein cholesterol by mean (± standard error) 41.0% ± 2.2% (P < .001), and the combination with diltiazem showed an additional reduction of 1.66% (95% confidence interval: -4.63 to 7.96, P > .05). The additional change in low-density lipoprotein cholesterol with diltiazem showed a nonsignificant positive correlation with the trough serum diltiazem concentration (R(2) = 0.142, P = .058). Co-administration of diltiazem 60 mg 3 times daily with simvastatin 20 mg daily tended to increase the changes in lipid parameters in these Chinese subjects, but the effects did not reach significance.
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
Joyce H S
JH
You
Winnie K Y
WK
Chan
Polly F P
PF
Chung
Miao
M
Hu
Brian
B
Tomlinson
D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D019540:Area Under Curve; D044466:Asian People; D008078:Cholesterol, LDL / Q000097:blood*; D018592:Cross-Over Studies; D004110:Diltiazem / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
D000959:Antihypertensive Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D004110:Diltiazem