Prisant L Michael, Elliott William J
Hypertension and Clinical Pharmacology Unit, Medical College of Georgia, Augusta, Georgia 30912, USA.
Clin Pharmacokinet. 2003;42(11):931-40. doi: 10.2165/00003088-200342110-00001.
Novel drug delivery systems are available in many areas of medicine. Their application in the treatment of hypertension continues to widen. Oral drug delivery systems permit antihypertensive agents that were previously administered two to four times daily to be administered once daily. Biotechnical use of chemical-dispensing systems has been applied to propranolol (polymer coated beads), clonidine (transdermal therapeutic system), nifedipine (osmotic pump and coat-core), isradipine (osmotic pump), verapamil (sodium alginate and spheroidal oral delivery absorption system), felodipine (coat-core), nisoldipine (coat-core) and diltiazem (polymer coated beads and Geomatrix. The initial goal was to lower blood pressure by a uniform amount throughout the entire day. Now, new drug delivery systems are being developed to target blood pressure in the early morning hours when most cardiovascular events occur. Two chronotherapeutic drug delivery systems are now available for verapamil (chronotherapeutic oral delivery absorption system and delayed coat osmotic pump). Disadvantages of sustained-release products include delayed achievement of pharmacodynamic effect, unpredictable bioavailability, enhanced first-pass hepatic metabolism, dose dumping, sustained toxicity, dosage inflexibility and increased cost. Potential advantages include reduced administration frequency, enhanced adherence and convenience, reduced toxicity, stable drug concentrations, uniform drug effect, decreased cost (occasionally) and decreased daily dosage.
新型药物递送系统在医学的许多领域都有应用。它们在高血压治疗中的应用范围不断扩大。口服药物递送系统使以前每日需服用两到四次的抗高血压药物能够每日服用一次。化学给药系统的生物技术应用已应用于普萘洛尔(聚合物包衣珠)、可乐定(透皮治疗系统)、硝苯地平(渗透泵和包芯)、伊拉地平(渗透泵)、维拉帕米(海藻酸钠和球形口服给药吸收系统)、非洛地平(包芯)、尼索地平(包芯)和地尔硫䓬(聚合物包衣珠和Geomatrix)。最初的目标是在一整天内使血压均匀下降。现在,正在开发新的药物递送系统,以针对大多数心血管事件发生的清晨时段的血压。目前有两种时辰治疗药物递送系统可用于维拉帕米(时辰治疗口服给药吸收系统和延迟包衣渗透泵)。缓释产品的缺点包括药效学作用延迟实现、生物利用度不可预测、首过肝代谢增强、剂量倾泻、持续毒性、剂量灵活性差和成本增加。潜在的优点包括给药频率降低、依从性和便利性提高、毒性降低、药物浓度稳定、药物作用均匀、成本降低(偶尔)和每日剂量减少。