Carter B L
Department of Pharmacy Practice, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
Am J Health Syst Pharm. 1998 Nov 15;55 Suppl 3:S17-23. doi: 10.1093/ajhp/55.suppl_3.S17.
The role of chronotherapeutics--agents that match drug delivery to the natural circadian rhythms of the cardiovascular system--in antihypertensive and antianginal therapy is discussed. Hypertension and angina remain two of the most important risk factors for cardiovascular morbidity and mortality. Early-morning increases in blood pressure do not seem to be attenuated by many currently available sustained-release and extended-dosing formulations of anti-hypertensive agents, such as atenolol, enalapril, sustained-release verapamil, nitrendipine, nifedipine, diltiazem, and long-acting propranolol. A 24-hour controlled-onset, extended-release delivery system (COER-24) for verapamil hydrochloride has recently been developed to address the pharmacokinetic and circadian challenges to controlling blood pressure and angina. COER-24 for verapamil hydrochloride, the first chronopharmacologic agent approved for the treatment of both hypertension and angina, is designed for bedtime administration. It provides the highest concentration of drug in the blood during the early hours of the day, when blood pressure and heart rate are rising rapidly. COER-24 for verapamil hydrochloride has a more favorable adverse-effect profile than is seen with immediate-release verapamil. COER-24 for verapamil hydrochloride provides effective blood pressure reduction for 24 hours and protects against the early-morning increase in blood pressure; the drug has a more favorable adverse-effect profile than immediate-release verapamil.
本文讨论了时辰治疗学（即使药物递送与心血管系统的自然昼夜节律相匹配的药物）在抗高血压和抗心绞痛治疗中的作用。高血压和心绞痛仍然是心血管疾病发病率和死亡率的两个最重要危险因素。许多目前可用的抗高血压药物，如阿替洛尔、依那普利、缓释维拉帕米、尼群地平、硝苯地平、地尔硫䓬和长效普萘洛尔的缓释和延长给药制剂，似乎并未减弱清晨血压的升高。最近开发了一种用于盐酸维拉帕米的24小时控释、缓释给药系统（COER-24），以应对控制血压和心绞痛方面的药代动力学和昼夜节律挑战。用于盐酸维拉帕米的COER-24是首个被批准用于治疗高血压和心绞痛的时辰药理学药物，设计用于睡前给药。在一天的早些时候，当血压和心率迅速上升时，它能使血液中的药物浓度达到最高。与速释维拉帕米相比，用于盐酸维拉帕米的COER-24具有更有利的不良反应谱。用于盐酸维拉帕米的COER-24可有效降低血压24小时，并预防清晨血压升高；与速释维拉帕米相比，该药物具有更有利的不良反应谱。
