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The availability of orally administered nortriptyline


The availability of an orally administered drug may be defined as the fraction of the total dose that enters the blood. Three healthy subjects were given identical doses of nortriptyline hydrochloride (NT-HCl) by the oral and intramuscular routes. The availability was assessed by comparing the total areas under the NT plasma concentration-time curves produced by the two methods of administration. The concentrations of NT in plasma and blood were determined by gas chromatography — mass spectrometry and were found to be almost identical. The observed availability of NT in these subjects ranged between 56 and 70% (mean 64%). The availability predicted from the parenteral plasma levels (assuming an average hepatic blood flow of 1.7 l/min) differed from the observed availability in one subject, perhaps because of the known variation in liver blood flow between individuals. The gastrointestinal absorption of NT-HCl was complete, since the recovery of the main metabolite, 10-hydroxynortriptyline, was the same after the two routes of administration. Pharmacokinetic analysis of the data showed that there might exist interindividual differences in the apparent volume of distribution of NT, (Vd)β. There was no apparent relationship between the variations in availability of NT and “steady-state” plasma levels or the disposition plasma half-lives of the drug. The calculated (Vd)β and (t 1/2)β of NT for each subject were in good agreement with those obtained from a previous study of single oral does of NT.

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Alexanderson, B., Borgå, O. & Alván, G. The availability of orally administered nortriptyline. Eur J Clin Pharmacol 5, 181–185 (1973).

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Key words

  • Tricyclic antidepressant
  • nortriptyline
  • single-dose kinetics
  • plasma/blood concentrations
  • metabolites
  • absorption
  • availability
  • apparent volume of distribution
  • plasma/blood clearances
  • gas chromatography-mass spectrometry
  • man