Abstract
Imipramine hydrochloride (IMI) was administered to 12 healthy volunteers on three occasions in random sequence: 12.5 mg IV, 50 mg orally after overnight fast, and 50 mg orally 30 min after eating a standardized breakfast. IMI concentrations were measured by gas-liquid chromatography using nitrogen-phosphorous detection and pharmacokinetic and bioavailability parameters determined by iterative nonlinear least-squares regression analysis. After IV administration, mean kinetic variables were: volume of distribution, 21.0 l/kg; total clearance, 12.8 ml/min per kg, and elimination half-life, 21.2 h. Mean absolute bioavailability of IMI in the fasting state was 43.6%. When IMI was administered immediately after the standardized meal, absolute bioavailability was 44.1%. After oral administration, the time to peak IMI level was not changed by concurrent food ingestion (2.8 vs 3.2 h after dosage), and the peak IMI concentration was no different (35 vs 30 ng/ml). Thus concurrent food ingestion has no effect on IMI absolute bioavailability, peak concentration attained after oral dosing, or the time to peak concentration.
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References
Abernethy DR, Greenblatt DJ, Shader RI (1981) Tricyclic antidepressant determination in human plasma by gas-liquid chromatography using nitrogen-phosphorous detection. Pharmacology 23:57–63
Amsterdam J, Brunswick D, Mendels J (1980) The clinical application of tricyclic antidepressant pharmacokinetics and plasma levels. Am J Psychiatry 137:653–662
Anonymous (1959) Weights of insured persons in the United States associated with lowest mortality. Stat Bull Metrop Life Insur Co 40:Nov–Dec
Brinkshulte M, Breyer-Pfaff U (1979) Binding of tricyclic antidepressants and perazine to human plasma. Naunyn-Schmiedeberg's Arch Pharmacol 308:1–7
Brunswick DJ, Mendels J (1977) Reduced levels of tricyclic antidepressants in plasma from vacutainers. Comm Psychopharmacol 1:131–134
Evans GH, Nies AS, Shand DG (1973) The disposition of propranolol III: Decreased half-life and volume of distribution as a result of plasma binding in man, monkey, dog, and rat. J Pharmacol Exp Ther 186:114–122
Gram LF, Christiansen J (1975) First-pass metabolism of imipramine in man. Clin Pharmacol Ther 17:555–563
Greenblatt DJ, Koch-Weser J (1975) Clinical pharmacokinetics. N Engl J Med 293:702–705, 964–970
Jorgenson OS, Lober M, Christiansen J, Gram LF (1980) Plasma concentration and clinical effect of imipramine treatment of childhood enuresis. Clin Pharmacokinet 5:386–393
Kristensen CB, Gram LF (1982) Equilibrium dialysis for determination of protein binding in imipramine: evaluation of a method. Acta Pharmacol Toxicol 50:130–136
Kuhn R (1958) The treatment of depressive states with G22355 (imipramine hydrochloride). Am J Psychiatry 115:459–464
Loo JCK, Riegelman S (1970) Assessment of pharmacokinetic constants from post-infusion blood curves obtained after i.v. infusion. J Pharm Sci 59:53–55
Marquardt DW (1963) An algorithm for least-squares estimation of non-linear parameters. J Soc Ind Appl Math 11:431–441
McAllister RG (1982) Clinical pharmacology of slow channel blocking agents. Prog Cardiovasc Dis 25:83–102
Melander A, Danielson K, Schersten B, Wahlin E (1977a) Enhancement of the bioavailability of propranolol and metoprolol by food. Clin Pharmacol Ther 22:108–112
Melander A, Berlin-Wahlen A, Bodin NO, Danielson K, Gustafsson B, Lindgren S, Westerlund D (1977b) Bioavailability of d-propoxyphene, acetylsalicyclic acid, and phenazone in a combination tablet (Doleron): interindividual variation and influence of food intake. Acta Med Scand 202:119–124
Melander A, Danielson K, Hanson A, Rudell B, Schersten B, Thulin T, Wahlin E (1977c) Enhancement of hydralazine bioavailability by food. Clin Pharmacol Ther 22:104–107
Newton R (1981) The side effect profile of trazodone in comparison to an active control and placebo. J Clin Psychopharmacol 1 (6 Supp 1):895–935
Rawlins MD, Henderson DB, Hijab AR (1977) Pharmacokinetics of paracetamol (acetaminophen) after intravenous and oral administration. Eur J Clin Pharmacol 11:283–286
Schomerus M, Spiegelhalder B, Stieren B, Eichelbaum M (1976) Physiological disposition of verapamil. Cardiovase Res 10: 605–612
Shand DG, Kornhauser DM, Wilkinson GR (1975) Effects of route of administration and blood flow on hepatic drug elimination. J Pharmacol Exp Ther 195:424–432
Sjoqvist F, Bertilsson L, Asberg M (1980) Monitoring tricyclic antidepressants. Ther Drug Monit 2:85–93
Svensson CK, Edwards DJ, Mauriello PM, Barde SH, Foster AC, Middleton E, Lalka D (1983) Effect of food on hepatic blood flow: implications in the food effect phenomenon. Clin Pharmacol Ther 34:316–323
Usanis RA (1972) NLIN-Nonlinear least-squares estimate of parameters (Library Services Document No. LSR-089-1: Research Triangle Park, N.C., Triangle Universities Computation Center
Wagner JG (1975) Fundamentals of clinical pharmacokinetics. Drug Intelligence Publications Hamilton, Ill
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Abernethyl, D.R., Divoll, M., Greenblatt, D.J. et al. Absolute bioavailability of imipramine: Influence of food. Psychopharmacology 83, 104–106 (1984). https://doi.org/10.1007/BF00427432
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DOI: https://doi.org/10.1007/BF00427432