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Related Experiment Videos

Etintidine-propranolol interaction study in humans.

S M Huang1, H S Weintraub, T B Marriott

  • 1Research Laboratories, Ortho Pharmaceutical Corporation, Raritan, New Jersey 08869-0602.

Journal of Pharmacokinetics and Biopharmaceutics
|December 1, 1987
PubMed
Summary
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Etintidine HCl, a potent H2-blocker, significantly increases propranolol levels and prolongs its elimination half-life. This drug interaction study suggests etintidine impairs propranolol metabolism, similar to cimetidine.

Area of Science:

  • Pharmacology
  • Drug Metabolism and Disposition

Background:

  • Etintidine HCl is a potent histamine H2-receptor antagonist.
  • Drug interactions involving H2-blockers can alter the pharmacokinetics of co-administered medications.

Purpose of the Study:

  • To investigate the effect of etintidine HCl on the disposition of propranolol in healthy subjects.
  • To compare the pharmacokinetic profiles of propranolol and its metabolite 4-hydroxypropranolol when co-administered with etintidine or placebo.

Main Methods:

  • A double-blind, two-way crossover study involving 12 healthy subjects.
  • Subjects received either etintidine (400 mg) or placebo twice daily for 4 days.
  • On Day 4, subjects received a single oral dose of propranolol (40 mg) 30 minutes after the morning dose of etintidine or placebo.

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  • Plasma concentrations of propranolol and 4-hydroxypropranolol were measured up to 24 hours post-dose using HPLC.

    • Main Results:

    • Etintidine significantly increased the area under the concentration-time curve (AUC0-infinity) of propranolol by 573.5 vs. 146.4 ng.hr/ml (p = 0.0001).
    • Etintidine prolonged the elimination half-life of propranolol from 2.33 hr to 4.61 hr.
    • Etintidine also increased the AUC0-24 values (43.8 vs. 16.4 ng.hr/ml, p = 0.0028) and prolonged the elimination half-life (4.87 vs. 1.97 hr) of 4-hydroxypropranolol.

    Conclusions:

    • Etintidine HCl impairs the elimination of propranolol, similar to cimetidine.
    • Etintidine also affects the elimination of the active metabolite, 4-hydroxypropranolol.