Abstract
The usual dosage regimen of diltiazem (Tildiem) is 60 mg 3–4 times a day. A sustained-release formulation has been developed (Mono-Tildiem LP 300 mg) in order to allow a single daily administration. Two repeated dosing studies were performed in healthy volunteers. The absolute bioavailability of sustained-release diltiazem LP 300 mg was investigated using concomitant i.v. administration of 13C-labelled drug: absolute bioavailability of the “once a day” formulation was 35%. The second study compared sustained-release diltiazem LP 300 mg with the standard formulation of diltiazem. The results showed that the diltiazem plasma concentrations obtained after the LP formulation remained stable between 2 and 14 h after administration and were compatible with a once a day administration. Relative bioavailability of sustained-release diltiazem LP 300 mg was 79.3% compared with diltiazem. Therefore, a unitary dose of sustained-release diltiazem LP 300 mg was chosen as the dose equivalent to the daily dose administered with the standard diltiazem formulation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Rosenthal SJ, Ginsburg R, Lamb IH, Baim DS, Schroeder JS (1980) Efficacy of diltiazem for control of symptoms of coronary arterial spasm. Am J Cardiol 46:1027–1032
Chaffman M, Brogden RN (1985) Diltiazem: a review of its pharmacological properties and therapeutic efficacy. Drugs 29:387–454
Veterans Administration Co-operative Study Group on Anti-hypertensive Agents (1967). Effects of treatment on morbidity in hypertension: results in patients with diastolic blood pressure averaging 115 through 129 mmHg. JAMA 242:1028–1079
Gülker H, Thale J, Heuer H, Olbing B, Bender F (1984) Comparative antiarrhythmic and antifibrillatory action of diltiazem, verapamil and nifedipine in acute myocardial ischemia (abstract). Eur Heart J [Suppl] 5:143
Inouye IK, Massie BM, Benowitz N, Simpson P, Loge D (1984) Antihypertensive therapy with diltiazem and comparison with hydrochlorothiazide. Am J Cardiol 53:1588–1592
Maeda K, Takasugi T, Tsukano Y, Tanaka Y, Shiota K (1981) Clinical study on hypotensive effect of diltiazem hydrochloride. Pharmacol Ther Toxicol 19:47–55
Bianchetti G, Regazzi M, Rondanelli R, Ascalone V, Morselli PL (1991) Bioavailability of diltiazem as a function of the administered dose. Biopharm Drug Disp 12:391–401
Gomeni R (1984). An interactive program for individual and population pharmacokinetic parameter estimation. Comput Biol Med 14:25–34
Gibaldi M, Perrier D (1982) Pharmacokinetics. Dekker, New-York
Westlake WJ (1976) Symmetrical confidence intervals for bioequivalence trials. Biometrics 32:741–744
Murata K, Yamahara H, Kobayashi M, Noda K, Samejima M (1989) Pharmacokinetics of an oral sustained-release diltiazem preparation. J Pharm Sci 78:960–963
Ochs HR, Knüchel M. (1984) Pharmacokinetics and absolute bioavailability of diltiazem in humans. Klin Wochenschr 62:303–306
Thiercelin JF, Necciari J, Caplain H, Cournot A, Combes M, Desmolin H, Flouvat B (1990) Development and pharmacokinetics of a new sustained-release formulation of diltiazem. J Cardiovasc Pharmacol 16 [Suppl 1]:S31-S37
Höglund P, Nilsson LG (1989) Pharmacokinetics of diltiazem and its metabolites after single and multiple dosing in healthy volunteers. Ther Drug Monit 11:558–566
Höglund P, Nilsson LG (1989) Pharmacokinetics of diltiazem and its metabolites after repeated multiple-dose treatments in healthy volunteers. Ther Drug Monit 11:543–550
Morselli PL, Rovei V, Mitchard M, Durand A, Gomeni R, Larribaud J (1978) Pharmacokinetics and metabolism of diltiazem in man (observations on healthy volunteers and angina pectoris patients). In: New drug therapy with a calcium antagonist. Bing RJ (ed) Excerpta Medica; Amsterdam pp 152–167
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bianchetti, G., Dubruc, C., Rosenzweig, P. et al. Pharmacokinetics and bioavailability of a sustained-release diltiazem formulation (Mono-Tildiem LP 300 mg) after repeated administration in healthy volunteers. Eur J Clin Pharmacol 48, 259–264 (1995). https://doi.org/10.1007/BF00198308
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00198308