Pharmacokinetics of isosorbide dinitrate (ISDN) and brachial arterial hemo dynamics have been studied in 15 patients with sustained essential hypertension. The hemodynamic study was performed by using a pulsed Doppler device en abling evaluation of the diameter of the brachial artery with an error of less than 10%. After intravenous administration until plateau concentrations were reached, the ISDN infusion was stopped in order to study the disappearance curve of the drug and the pharmacokinetic parameters. ISDN caused a signifi cant decrease in systolic pressure, a significant increase in arterial diameter, and no change in heart rate. Brachial hemodynamics were not correlated with the plasma concentration in the steady state or the area under the disappear ance curve. In contrast, the changes in arterial diameter during perfusion were significantly correlated with the apparent distribution volume, a finding that might indirectly reflect the affinity of ISDN for vascular tissues.
Get full access to this article
View all access options for this article.
References
1.
Amstrong PW, Amstrong JA, Marks GS: Pharmacokinetic-hemodynamic studies of nitroglycerin ointment in congestive heart failure. Am J Cardiol46:670-677, 1980.
2.
Amstrong PW, Amstrong JA, Marks GS: Pharmacokinetic-hemodynamic studies of intravenous nitroglycerin in congestive heart failure. Circulation62:160-168, 1980.
3.
Fung AL, McNiff EF, Rugirello D., et al: Kinetics of isosorbide dinitrate and relationship to pharmacological effects. Br J Clin Pharmacol11:579-587, 1981.
4.
Thadani U., Manyari D., Parker JO, et al: Tolerance to the circulatory effects of oral isosorbide dinitrate. Rate of development and cross-tolerance to glyceryl trinitrate. Circulation61:526-532, 1980.
5.
Thadani U., Fung HL, Darke AC, and Parker JO: Oral isosorbide dinitrate in the treatment of angina pectoris. Dose response relationship and duration of action during acute therapy. Circulation62:491-506, 1980.
6.
Thadani U., Fung HL, Darke AC, Parker JO: Oral isosorbide dinitrate in angina pectoris: Comparison of duration of action and dose-response relation during acute and sustained therapy. Am J Cardiol49:411-422, 1982.
7.
Levenson JA, Peronneau PA, Simon A., Safar ME: Pulsed Doppler: Determination of diameter, blood flow velocity and volumic flow of brachial artery in man. Cardiovasc Res15:164-168, 1981.
8.
Safar M., Peronneau J., Levenson J., Simon A.: Pulsed Doppler: Diameter, velocity and flow of brachial artery in sustained essential hypertension. Circulation63:383-387, 1981.
9.
Simon Ach, Levenson JA, Levy BY, et al: Effect of nitroglycerin on peripheral large arteries in hypertension . Br J Clin Pharmacol14:241-244, 1982.
10.
Safar ME, Simon Ach, Levenson JA, and Cazor JL: Hemodynamic effects of diltiazem in hypertension. Circ Res52 (part 2) 1:169-174, 1983.
11.
Laufen H., Scharpf F., Bartsch G.: Improved method for the rapid determination of isosorbide dinitrate in human plasma and its application in pharmacokinetic studies. J Chromatogr146:457-464, 1978.
12.
Frydman A., Levenson J., Simon Ach, et al: Pharmacocinétique du dinitrate d'isosorbide: Approche après perfusion intraveineuse chez le patient hypertendu. NouvPresse Méd27:2049-2054, 1982.
13.
Fung HL, McNiff EF, Rugirello D., et al: Kinetics of isosorbide dinitrate and relationships to pharmacological effects. Br J Clin Pharmacol11:579-586, 1981.
14.
Gibaldi M., Perrier D.: Pharmacokinetics, ed. 2. New York, Bâsle, Marcel Dekker Inc, 1982.
15.
BMDP Statistical Software, ed. by Dixon WJ.Berkeley, Los Angeles, London, Univ. of California Press, 1981, pp. 1-270.
16.
Snedecor GW: Statistical Methods. Ames, Iowa, The Iowa State University Press, 1962, pp. 5-322.
17.
Hastings Naj, Peacock JB: Statistical Distributions. New York, Wiley, 1975, pp. 12-126.
18.
Snedecor GW, Cochran WG: Statistical Methods, ed. 7. Ames, Iowa, The Iowa State University Press, 1980, pp. 21-178.
19.
Brown J., Forsythe S.: Robust tests of quality of variances. J Am Statis Assoc69:364-378, 1974.
20.
Schnaar RL, Sparks HV: Response of large and small coronary arteries to nitroglycerin, NaNo 2 and adenosine. Am J Physiol223:223-229, 1972.
21.
Reed DE, Akester JM, Prather JF, et al: Blood and tissue levels of 14C-isosorbide dinitrate after oral and intravenous administration to rat. J Pharmacol Exp Ther202:32-41, 1977.
22.
Frydman A., Gaillot J., Levenson J.: Etude pharmacocinétique du dinitrate d'isosorbide après perfusion intraveineuse chez l'hypertendu: apport de l'analyse statistique multivariate à l'interprétation des résultats. Proceedings of the 1 st European Congress of Biopharmaceutics and Pharmacokinetics 3:93, 1981.
23.
Taylor T., Chasseaud LF, Doyle E., et al: Isosorbide dinitrate pharmacokinetics. Arzeim Forsch/ Drug Res32:1329-1337, 1982.
24.
Morrison RA , Fung HL, Höhmann D., et al: Isosorbide dinitrate: Pharmacokinetics after intravenous administration. J Pharm Sci71:721-729, 1982.
25.
Morrison RA , Wiegand VW, Jähnchen E., et al: Isosorbide dinitrate kinetics and dynamics after intravenous, sublingual and percutaneous dosing in angina. Clin Pharmacol Ther6:747-756, 1983.
26.
Fung HL, Sutton SC, Kamiya A.: Blood vessel uptake in the rat. J Pharmacol Exp Ther228:334-341, 1984.
27.
Simon Ach, Safar ME, Kheder AM, et al: Systolic hypertension: Hemodynamic mechanisms and choice of antihypertensive treatment. Am J Cardiol44:505-511, 1979
