Summary
The disposition of aprindine following a single oral dose can best be described by a two-compartment open model. The mean plasma half-life (t1/2β) increased from 8.0±2.1 h (SD) after a 25 mg dose to 9.4±2.9 h after 50 mg and to 15.8±2.6 h after 100 mg, with a decrease in total plasma clearance (Cl/F) and volume of distribution at steady state (Vdss/F) and during β-phase (Vdβ/F). The area under plasma concentration-time curve (AUC), maximum plasma concentration (Cmax) and the amount of unchanged aprindine excreted in the urine increased in a non-linear fashion with the increase in dose. The t1/2β after multiple oral doses showed a 3-fold increase over the single dose value. These results indicate that aprindine shows dose-dependent non-linear kinetics.
This is a preview of subscription content, log in via an institution to check access.
References
Kesteloot H, Van Mieghem W, De Geest H (1973) Aprindine (AC 1802). A new antiarrhythmic drug. Acta cardiol (Brux) 28: 145–165
Fasola AF, Carmichael R (1974) The pharmacology and clinical evaluation of aprindine — a new antiarrhythmic agent. Acta Cardiol (Brux) 18 [Suppl]: 317–333
Danilo P (1979) Aprindine. Am Heart J 97: 119–124
Zeipes DP, Elharrar V, Gilmour RF, Heger JJ, Prystowsky EN (1980) Studies with aprindine. Am Heart J 100: 1055–1062
Stoel I, Hagemeijer SF (1980) Aprindine: a review. Eur Heart J 1: 147–156
Van Durme JP, Bogaert MJ, Rosseel MT (1974) Therapeutic effectiveness and plasma levels of aprindine, a new antidysrhythmic drug. Eur J Clin Pharmacol 7: 343–346
Dodion L, Suray JM, Deblecker M, Georges A (1974) Caracteristiques pharmacocinetiques et biodegradation de l'aprindine chez l'homme. Therapie 29: 221–232
Murphy PJ (1974) Metabolic pathways of aprindine. Acta Cardiol (Brux) 18 [Suppl]: 131–142
Delcroix C, Martin L, Van Durme JP, Kesteloot H, Hagemeijer F, Mbuyamba P, Deblecker M (1974) Model for exchange kinetics of aprindine in man after single and multiple doses. Acta Cardiol (Brux) 18 [Suppl]: 177–194
Ito T, Namekawa H, Kobari T (1983) Determination of aprindine in plasma by gas chromatography-mass spectrometry. J Chromatogr 274: 341–345
Brown RD, Manno JE (1978) ESTRIP, a BASIC computer program for obtaining initial polyexponential parameter estimates. J Pharm Sci 67: 1687–1691
Wagner JG (1975) Fundamentals of Clinical pharmacokinetics. Drug Intelligence Publications, Hamilton, Ill, USA
Perrier D, Ashley JJ, Levy G (1973) Effects of product inhibition on kinetics of drug elimination. J Pharmacol Biopharm 1: 231–241
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kobari, T., Itoh, T., Hirakawa, T. et al. Dose-dependent pharmacokinetics of aprindine in healthy volunteers. Eur J Clin Pharmacol 26, 129–131 (1984). https://doi.org/10.1007/BF00546721
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00546721