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J Clin Pharmacol ; 47(12): 1555-69, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18048574

ABSTRACT

Guidelines stress the importance of the simultaneous management of multiple cardiovascular risk factors. This can in part be achieved by coadministration of lipid-lowering and antihypertensive treatments. Potential pharmacodynamic interaction between drugs should be investigated as part of developing single-pill combinations. The Respond trial assessed whether combining amlodipine to treat hypertension and atorvastatin to treat dyslipidemia affected the action of either monotherapy. A total of 1660 hypertensive patients with dyslipidemia received 1 of 15 combinations of amlodipine (placebo, 5, or 10 mg) and atorvastatin (placebo, 10, 20, 40, or 80 mg) in a 3 x 5 factorial randomized, placebo-controlled design. At 8 weeks, combination-treated patients experienced dose-related and statistically significant reductions in systolic blood pressure, low-density lipoprotein cholesterol, and Framingham risk score. Overall, coadministered atorvastatin and amlodipine was well tolerated and without adverse pharmacodynamic interaction; combination treatment did not affect the low-density lipoprotein cholesterol-lowering efficacy and safety of atorvastatin, or the systolic blood pressure-lowering efficacy and safety of amlodipine.


Subject(s)
Amlodipine/therapeutic use , Dyslipidemias/drug therapy , Heptanoic Acids/therapeutic use , Hypertension/drug therapy , Pyrroles/therapeutic use , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Amlodipine/adverse effects , Amlodipine/pharmacokinetics , Anticholesteremic Agents/adverse effects , Anticholesteremic Agents/pharmacokinetics , Anticholesteremic Agents/therapeutic use , Antihypertensive Agents/adverse effects , Antihypertensive Agents/pharmacokinetics , Antihypertensive Agents/therapeutic use , Aspartate Aminotransferases/blood , Atorvastatin , Blood Pressure/drug effects , Cholesterol, LDL/blood , Dose-Response Relationship, Drug , Double-Blind Method , Drug Interactions , Drug Therapy, Combination , Dyslipidemias/blood , Dyslipidemias/complications , Female , Heptanoic Acids/adverse effects , Heptanoic Acids/pharmacokinetics , Humans , Hypertension/complications , Hypertension/physiopathology , Male , Pyrroles/adverse effects , Pyrroles/pharmacokinetics , Treatment Outcome , gamma-Glutamyltransferase/blood
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