Abstract
Pharmacokinetic profiles of imipramine and a newer tetracyclic antidepressant, maprotiline, were studied in elderly (75–83 years of age) subjects who were given a single oral dose of 125 and 175 mg, respectively, of these drugs. The apparent elimination half-life of imipramine was 20.8–34.9 h (mean 26.4 h), its biovailability (F) was 40–64% (mean 57%), and the apparent plasma clearance was from 0.27–0.57 h/kg (mean 0.41 h/kg). Maprotiline had a longer half-life (mean 31.5 h range 20.6–51.8 h, but its bioavailability (mean 50%) and plasma clearance (mean 0.49 h/kg) values were in the range similar to those seen after imipramine. It appears that the elimination half-life of imipramine is longer and its plasma clearance is markedly reduced in elderly subjects when compared to values reported in young adults. Subjective clinical side effects were minimal with the two drugs. However, alterations in heart rate, blood pressure, or electrocardiogram occurred in all subjects. This suggests that caution should be exercised before initiating and during the treatment of elderly patients with these antidepressant drugs.
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References
Ban TA: (1978) The treatment of depressed geriatric patients. Am J Psychiatry 32:93–104
Bianchetti G, Bonaccorsi A, Chiodaroli A, Franco R, Garattini S, Gomeni R, Morselli PL (1977) Plasma concentrations and cardiotoxic effects of desipramine and protriptyline in the rat. Br J Pharmacol 60:11–19
Carr AC, Hobson RP (1977) High serum concentration of antidepressants in elderly patients BR Med J 2:1151
Gibaldi M, Boyes RN, Feldman S (1971) Influence of first-pass effect on availability of drugs on oral administration. J Pharm Sci 60:1338–1340
Gomeni C, Gomeni R (1978) IGPHARM: Interactive graphic package for pharmacokinetic analysis. Comput Biomed Res 11:345–361
Gram LF, Andreasen PB, Overo KF, Christiansen J (1976) Comparison of single-dose kinetics of imipramine, nortriptyline and amitriptyline in man. Psychopharmacology 50:21–27
Gram LF, Christiansen J: (1975) First-pass metabolism of imipramine in man. Clin Pharmacol Ther 17:555–563
Henry JF, Altamura C, Gomeni R, Hervy MP, Forette F, Morselli PL (1980) Pharmacokinetics of amitriptyline in the elderly. Int J Clin Pharmacol Biopharm, in press
Jones RB, Luscombe DK Single dose study with maprotiline in normal subjects. Jukes A (ed) Depression: The biochemical and physiological role of ludiomil, CIBA 1977, p 135
Kantor JS, Glassman AH, Bigger JT, Perel JM, Giardina EV (1978) The cardiac effects of therapeutic plasma concentration of imipramine. Am J Psychiatry 135:534–538
Morselli, PL, Placidi GF (1977) Terapia farmacologica nel soggetto anziano: aspetti farmacocinetici. In: A Muratorio, C Maggini, L Murri, eds. II sonno nell'età senile. Pacini, Pisa p 61
Nagy A, Johanson R (1975) Plasma levels of imipramine and desipramine in man after different routes of administration. Naunyn Schmiedebergs. Arch. Pharmacol 290:145–160
Nies A, Robinson DS, Friedman MJ, Green R, Cooper TB, Ravaris CL, Ives JO (1977) Relationship between age and tricyclic antidepressant plasma levels. Am J Psychiatry 134:790–793
Rasmussen J (1965) Amitriptyline and imipramine poisoning. Lancet II:850–851
Riegelman A, Loo J, Rowland M (1968) Concept of a volume of distribution and possible errors in evaluation of this parameter. J Pharmaceut Sci 57:128–133
Reiss W, Rajagopalan TG, Keberle H (1972) The metabolism and pharmacokinetics of Ludiomil (maprotiline). In: Kielholz P ed. Depressive illness. Diagnosis, assessment, treatment, Hans Huber Bern p 140
Rovei V, Sanjuan M, Hrdina PD (1980) Analysis of tricyclic antidepressant drugs by gas chromatography using NPD detection with packed and capillary columns. J Chromatogr 182: 349–357
Shader RI, Greenblatt DJ (1979) Pharmacokinetics and clinical drug effects in the elderly. Psychopharmacol Bull 15:8–16
Sherlock S, Bearn AG, Gilling BH, Paterson JCS (1950) Splanchnic blood flow in man by the bromsulfalein method. The relation of peripheral plasma bromsulfalein level to the calculated flow. J Lab Clin Med 35:923–932
Vohra J, Burrows G, Hunt D, Sloman G (1975) The effect of toxic and therapeutic doses of tricyclic antidepressant drugs on intracardiac conduction. Eur J Cardiol 3:219–227
Wagner JC (1975) Fundamentals of clinical pharmacokinetics. Hamilton: Drug Intelligence
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Hrdina, P.D., Rovei, V., Henry, J.F. et al. Comparison of single-dose pharmacokinetics of imipramine and maprotiline in the elderly. Psychopharmacology 70, 29–34 (1980). https://doi.org/10.1007/BF00432366
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DOI: https://doi.org/10.1007/BF00432366