Summary
The chronic oral administration of 0.07 mg digitoxin o. d. for up to 58 days to 12 healthy volunteers caused a small drop in mean heart rate HR (95 % CI: −7.9 to −1.6 beats · min−1), in mean diastolic blood pressure (95 % CI: −8.3 to −0.4 mm Hg), shortening of the QTc-interval (95 % CI: −42 to −19 ms), shortening of the HR-corrected pre-ejection period PEPc (95 % CI: −16 to −1 ms) and electromechanical systole QS2c (95 % CI: −25 to −1 ms), and an increase in the impedance cardiographic Heather index (dZ/dtmax/RZ, 95 % CI: 0.3 to 4.3) relative to the baseline measurements before digitalisation.
The concomitant administration of 25 mg oral captopril b. d. did not significantly alter these responses relative to the concomitant double-blind administration of placebo, nor did it alter the pharmacokinetic characteristics of plasma digitoxin at steady state.
Thus, no relevant change in the pharmacokinetic and pharmacodynamic characteristics of chronically administered digitoxin were induced by concomitant treatment with captopril.
References
Breithaupt K, Erb KA, Neumann B, Wolf GK, Belz GG (1990) Comparison of four noninvasive techniques to measure stroke volume: dual beam Doppler echoaortography, electrical impedance cardiography, mechanosphygmography and M-mode echocardiography of the left ventricle. Am J Noninvasiv Cardiol 4:203–209
Bazett HC (1920) An analysis of the time relations of the electrocardiogram. Heart 7:353–370
Weissler AM, Harris WS, Schoenfeld CD (1968) Systolic time intervals in heart failure in man. Circulation 37:149–159
Kubicek WG, Karnegis JN, Patterson RP, Witsoe DA, Mattson RH (1966) Development and evaluation of an impedance cardiac output system. Aerosp Med 37:1208–1212
Hill DW, Merrifield AJ (1976) Left ventricular ejection and the Heather Index measured by non-invasive methods during postural change in man. Acta Anaesth Scand 20:313–320
Siegel JH, Fabian M, Lankau C, Levine M, Cole A, Nahmad M (1970) Clinical and experimental use of thoracic impedance plethysmography in quantifying myocardial contractility. Surgery 57:907–917
Belz GG, Riedlinger G (1980) Nichtinvasive Untersuchungen zur kardialen Wirkung niedriger Digitoxin-Erhaltungsdosen. Z Kardiol 69:296–306
Schuirmann DJ (1987) A comparison of the two one-sided test procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm 15: 657–680
Mey C de, Brendel E, Enterling D (1990) Carvedilol increases the systemic bioavailability of oral digoxin. Br J Clin Pharmacol 29:486–490
Amman EM, Arnold HD, Friedman TL, Smith TW (1987) Pharmacokinetic drug interactions between digoxin and antiarrhythmic agents and calcium channel blocking agents: an appraisal of study methodology. Cardiovasc Drug Ther 1:183–189
Belz GG, Doering W, Munkes R (1981) Effects of various calcium-antagonists on blood level and renal clearance of digoxin. Circulation 64 [Suppl. IV]:24
Belz GG, Aust PE, Munkes R (1981) Digoxin plasma concentrations and nifedipine. Lancet 1:844–845
Belz GG, Erbel R, Schumann K, Gilfrich HJ (1978) Doseresponse relationships and plasma concentrations of digitalis glycosides in man. Eur J Clin Pharmacol 13:103–111
Belz GG, Aust PE, Schneider B (1981) Time course of the effects of single intravenous doses of digitoxin in normal volunteers. J Cardiovasc Pharmacol 3:1116–1125
Miyakawa T, Shionoiri H, Takasaki I, Kobayashi K, Ishii M (1991) The effect of captopril on pharmacokinetics of digoxin in patients with mild congestive heart failure. J Cardiovasc Pharmacol 17:576–580
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
de Mey, C., Elich, D., Schroeter, V. et al. Captopril does not interact with the pharmacodynamics and pharmacokinetics of digitoxin in healthy man. Eur J Clin Pharmacol 43, 445–447 (1992). https://doi.org/10.1007/BF02220626
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02220626