Artículos de revistas
Bioequivalence Study Of Two Enalapril Maleate Tablet Formulations In Healthy Male Volunteers: Pharmacokinetic Versus Pharmacodynamic Approach
Registro en:
European Journal Of Clinical Pharmacology. , v. 50, n. 5, p. 399 - 405, 1996.
316970
10.1007/s002280050130
2-s2.0-0029945370
Autor
Ribeiro W.
Muscara M.N.
Martins A.R.
Moreno Jr. H.
Mendes G.B.
De Nucci G.
Institución
Resumen
Objective: Two different conventional release enalapril maleate tablet formulations were evaluated for their relative bioavailability (Eupressin tablets 10 mg, Biosintetica as the test formulation vs Renitec tablets 10 mg Merck Sharp and Dhome, as the reference formulation). A single 20 mg oral dose of each preparation was administered to 18 healthy male adult volunteers and their bioequivalence was assessed by comparing the serum enalaprilat and total enalapril (enalaprilat plus enalapril maleate) concentration-time curves. Angiotensin converting enzyme (ACE) activity was also quantified in each serum sample. Results: The pharmacokinetic parameters obtained for each formulation were the area under the time-concentration curve from 0 to 24 h (AUC[0-24]), maximum concentration C(max) and the time at which it occurred (t(max)). When serum enalaprilat concentration-time curves were employed to assess bioequivalence, the formulations were bioequivalent in the extent but not in the rate of absorption. However, no difference in either the extent or the rate of absorption were observed when serum total enalapril vs time curves were analysed. ACE activity-time curves were similar for both formulations and showed that ACE was 90% inhibited 3-5 h after enalapril administration, and till approximately 50% after 24 h. At that time, circulating enalaprilat and total enalapril levels were less than the tenth of C(max). Conclusion: The results show that complete bioequivalence of the two formulations can be concluded from serum total enalapril concentration data, and that serum ACE activity is not a suitable pharmacodynamic variable for assessing bioequivalence. 50 5 399 405 Todd, P.A., Goal, K.I., Enalapril: A reappraisal of its pharmacology and therapeutic use in hypertension (1992) Drugs, 43, pp. 346-383 Todd, P.A., Heel, R.C., Enalapril: A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure (1986) Drugs, 31, pp. 198-248 Ferguson, R.K., Vlasses, P.H., Swanson, B.N., Mojaverian, P., Hichens, M., Effects of enalapril, a new converting enzyme inhibitor, in hypertension (1982) Clin Pharmacol Ther, 32, pp. 48-53 Sánchez, R.A., Marcó, E., Gilbert, H.B., Raffaele, P., Brito, M., Moledo, L.I., Natriuretic effect and changes in renal haemodynamics induced by enalapril in essential hypertension (1985) Drugs, 30 (1 SUPPL.), pp. 49-58 Sánchez, R.A., Ramírez, A.J., Muscará, M.N., Gilbert, H.B., Marcó, E., Moledo, L.I., Inhibitory effects of enalapril on serum aldosterone in essential hypertension (1987) Medicina (Bs. As.), 47, pp. 256-260 Sybertz, E.J., Baum, T., Ahn, H.S., Nelson, S., Eynon, E., Angiotensin converting enzime inhibitor activity of SCH 31846, a new non-sulfhydryl inhibitor (1983) J Cardiovasc Pharmacol, 5, pp. 643-654 Hui, S.C.G., Dai, S., Ogle, C.W., Potentiation of depressor responses to arachidonic acid by angiotensin converting enzyme inhibitors in the rat (1984) Clin Exp Pharmacol Physiol, 11, pp. 621-625 Patchett, A.A., Harris, E., Tristram, E.W., Wyavratt, M.J., Wu, M.T., Taub, D., Peterson, E.R., Stone, C.A., A new class of angiotensin-converting enzyme inhibitors (1980) Nature, 288, pp. 280-283 Kelly, J.G., O'Malley, K., Clinical pharmacokinetics of the newer ACE inhibitors, a review (1990) Clin Pharmacokinet, 19, pp. 177-196 MacFadyen, R.J., Meredith, P.A., Elliot, H.L., Enalapril clinical pharmacokinetics and pharmacokinetic-pharmacodynamic relationships (1993) Clin Pharmacokinet, 25, pp. 274-282 Donelly, R., Meredith, P.A., Elliot, H.L., Reid, J.L., Kineticdynamic relations and individual responses to enalapril (1990) Hypertension, 15, pp. 301-309 Weisser, K., Schloos, J., Lehmann, K., Düsing, R., Vetter, H., Mutschler, E., Pharmacokinetics and converting enzyme inhibition after morning and evening administration of oral enalapril to healthy subjects (1991) Eur J Clin Pharmacol, 40, pp. 95-99 Witte, K., Weisser, K., Neubeck, M., Mutschler, E., Lehman, K., Hopf, R., Lemmer, B., Cardiovascular effects, pharmacokinetics and converting enzyme inhibition of enalapril after morning versus evening administration (1993) Clin Pharmacol Ther, 54, pp. 177-186 Dzau, V.J., Circulation versus local renin-angiotensin system in cardiovascular homeostasis (1988) Circulation, 77 (1 SUPPL.), pp. 11-14 Falkenhahn, M., Gohlke, P., Paul, M., Stoll, M., Unger, T., The renin-angiotensin system in the heart and vascular wall: New therapeutic aspects (1994) J Cardiovasc Pharmacol, 24, pp. S6-S13 Hichens, M., Hand, E.L., Mulcahy, W.S., Radioimmunoassay for angiotensin converting enzyme inhibitors (1981) Ligand Q, 4, p. 43 Cushman, D.W., Cheung, H.S., Spectrophotometric assay and properties of the ACE of rabbit lung (1970) Biochem Pharmacol, 20, pp. 1637-1648 Hurst, P.L., Lovell-Smith, C.J., Optimized assay for serum ACE activity (1981) Clin Chem, 27, pp. 2048-2052 Hauschke, D., Steinijans, V.W., Diletti, E., A distribution-free procedure for the statistical analysis of bioequivalence studies (1990) Int J Clin Pharmacol Ther Toxicol, 28, pp. 72-78 (1985) Bioavailability and Bioequivalence Requirements, (320 PART), pp. 154-173. , Food and Drug Administration, 4-1- Edition. Federal Register In vivo bioequivalence guidances (1993) Pharmacopeial Forum, 19, pp. 6501-6508 Larmour, I., Jackson, B., Cubela, R., Johnston, C.I., Enalapril (MK421) activation in man: Importance of liver status (1985) Br J Clin Pharmacol, 19, pp. 701-704 Ohnishi, A., Tsuboi, Y., Ishizaki, T., Kubota, K., Ohno, T., Yoshida, H., Kanezaki, A., Tanaka, T., Kinetics and dynamics of enalapril in patients with liver cirrhosis (1989) Clin Pharmacol Ther, 45, pp. 657-665