COMPARISON OF PHARMACOKINETICS AND PHARMACODYNAMICS OF THE ORIGINAL AND GENERIC ENALAPRIL IN THE ELDERLY PATIENTS WITH ARTERIAL HYPERTENSION

Aim. To study the pharmacokinetic, pharmacodynamic and pharmacoeconomic parameters of the original and generic enalaprils in the treatment of the elderly patients with hypertension (HT). Material and Methods. Patients (n=40) 75–90 years with HT were included in the open randomized comparative study. Patients were randomized into two groups. Patients of the group 1 received generic enalapril, patients of the group 2 — the original enalapril consisting of combined therapy. Pharmacokinetic single-dose study of original and generic enalapril were carried out with high-performance liquid chromatography. Pharmacodynamic study was carried out in single-dose administration as well as after 2 and 4 weeks of treatment with original and generic enalapril. Pharmacoeconomic evaluation of antihypertensive drugs was carried out on the basis of cost minimization analysis. Results. Original enalapril dose necessary to achieve the target blood pressure (BP) was 10 mg/day as a part of two-component therapy. This for generic enalapril was 20 mg/day consisting of three- or four-component therapy. Both drugs have shown an acceptable safety profile. Pharmacokinetic differences were revealed between original and generic enalapril: area under pharmacokinetic curve 204.14 (202.25–206.05) vs 136.23 (134.17–137.65) ng*h/ml, respectively; time of the drug retention in the blood plasma 5.42 (5.26–5.76) vs 4.88 (4.86–4.94) hours, respectively; p<0.001. Original enalapril demonstrated more stable 24-hour antihypertensive effect in once daily administration in comparison with this in generic enalapril: trough/peak ratio 78.67% (47.61–91.35%) vs 44.96% (32.44–55.49%), respectively , p<0.01. The average daily cost of combined therapy containing generic enalapril was 15.91 rubles per patient, while this in combined therapy containing original enalapril — 13.78 rubles per patient. Conclusion. Medicines on the basis of original and generic enalapril have pharmacokinetic, pharmacodynamic and pharmacoeconomic differences.

1. Safarova G.L. Demography of aging: current status and research priorities. Uspekhi Gerontologii 2009; (1): 49–59. Russian (Сафарова Г .Л. Демография старения: современное состояние и приоритетные направления исследований. Успехи геронтологии 2009; (1): 49–59).

2. Marcevich S.Ju., Shal'nova S.A, Kutishenko N.I. The study of the clinical equivalence of the two drugs enalapril in hypertensive patients. Rossiyskiy Kardiologicheskiy Zhurnal 2003; (5): 68–71. Russian (Марцевич С.Ю., Шальнова С.А, Кутишенко Н.И. Изучение клинической эквивалентности двух препаратов эналаприла у больных артериальной гипертонией. Российский кардиологический журнал 2003; (5): 68–71).

3. Jakusevich V.V. Assessment of the quality of generic drugs in cardiology: realities and possibilities. Rational Pharmacoter Cardiol 2005; (1): 13–18. Russian (Якусевич В.В. Оценка качества препаратов- дженериков в кардиологии: реалии и возможности. Рациональная фармакотерапия в кардиологии 2005; 1:13–18).

4. Waeber B, Erne P , Saxenhofer H, et al. Use of drugs with more than 24-hour duration of action. J Hypertens 1994;12 (8):67–71.

5. National Kidney Foundation. K/DOQI Clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39(1): SI—266.

6. Ostroumova O.D., Bondarec O.V., Shorikova E.G. Treatment of hypertension: comparison klinicheskoyi cost-effectiveness of original and generic drugs. Sistemnye Gipertenzii 2008; (4): 18–21. (Остроумова О.Д., Бондарец О.В., Шорикова Е.Г . Лечение артериальной гипертонии: сравнение клинической и экономической эффективности оригинальных и генерических препаратов. Системные Гипертензии 2008; (4): 18–21).

7. Nedogoda S.V., Marchenko I.V., Chaljabi T .A. Sravnitel'naja antigipertenzivnaja jeffektivnost' generikov ingibitora angiotenzinprevrawajuwego fermenta jenalaprila-reniteka (jenapa, jednita, invorila, jenvasa i jenama) i stoimost' lech Comparative antihypertensive efficacy of generic ACE inhibitor enalapril, renitek (Enap, ednita, invorila, envasa and Enam) and the cost of treatment in patients with essential hypertension. Arterial'naja gipertenzija 2000; (1): 52–54. Недогода С.В., Марченко И.В., Чаляби Т .А. Сравнительная антигипертензивная эффективность генериков ингибитора ангиотензинпревращающего фермента эналаприла-ренитека (энапа, эднита, инворила, энваса и энама) и стоимость лечения у больных гипертонической болезнью. Артериальная гипертензия 2000; 1: 52–54.

8. Conducting qualitative research bioequivalence of drugs. Methodical instructions. Moscow: Ministry of Health of the Russian Federation; 2004 Russian (Проведение качественных исследований биоэквивалентности лекарственных средств. Методические указания. М.: МЗ и СР РФ; 2004).