Dose-dependent Kinetics of Imipramine in Elderly Patients

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 1981 Jan 1

PMID 6803279

Citations 13

Authors

M Bjerre

L F Gram

P Kragh-Sorensen

C B Kristensen

O L Pedersen

M Moller

P Thayssen

Affiliations

Soon will be listed here.

Abstract

In a group of elderly depressed patients treated with imipramine (50-200 mg/day), six patients had the dose changed after 1-3 weeks of treatment. In all cases an increased dose resulted in a considerably disproportional rise in the plasma level of the active metabolite desipramine. In a group of elderly depressed patients treated with nortriptyline (40-100 mg/day) the dose/plasma level ratio could be examined in 6 patients, and there was no tendency towards a disproportional rise in plasma level, when the dose was raised. Dose changes, thus, may result in unpredictable changes in plasma levels during imipramine treatment and therapy control by plasma level monitoring may be difficult in these patients. Additional treatment with perphenazine (8-16 mg/day) to patients on imipramine (N = 3) or nortriptyline (N = 2) caused a marked rise in drug levels for imipramine in particular affecting the desipramine levels.

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References

Hamilton M . Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol. 1967; 6(4):278-96. DOI: 10.1111/j.2044-8260.1967.tb00530.x. View

Gram L . Factors influencing the metabolism of tricyclic antidepressants. Studies on interactions and first pass elimination. Dan Med Bull. 1977; 24(3):81-9. View

Nagy A, Treiber L . Quantitative determination of imipramine and desipramine in human blood plasma by direct densitometry of thin-layer chromatograms. J Pharm Pharmacol. 1973; 25(8):599-603. DOI: 10.1111/j.2042-7158.1973.tb10644.x. View

Gram L, Overo K . Drug interaction: inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man. Br Med J. 1972; 1(5798):463-5. PMC: 1787494. DOI: 10.1136/bmj.1.5798.463. View

von Bahr C, Orrenius S . Spectral studies on the interaction of imipramine and some of its oxidized metabolites with rat liver microsomes. Xenobiotica. 1971; 1(1):69-78. DOI: 10.3109/00498257109044380. View

Brunswick D, Amsterdam J, MENDELS J, Stern S . Prediction of steady-state imipramine and desmethylimipramine plasma concentrations from single-dose data. Clin Pharmacol Ther. 1979; 25(5 Pt 1):605-10. DOI: 10.1002/cpt1979255part1605. View

Glassman A, Perel J, Shostak M, Kantor S, Fleiss J . Clinical implications of imipramine plasma levels for depressive illness. Arch Gen Psychiatry. 1977; 34(2):197-204. DOI: 10.1001/archpsyc.1977.01770140087010. View

Kragh-Sorensen P, Hansen C, BAASTRUP P, Hvidberg E . Self-inhibiting action of nortriptylin's antidepressive effect at high plasma levels: a randomized double-blind study controlled by plasma concentrations in patients with endogenous depression. Psychopharmacologia. 1976; 45(3):305-12. DOI: 10.1007/BF00421145. View

Kragh-Sorensen P, Larsen N . Factors influencing nortriptyline steady-state kinetics: plasma and saliva levels. Clin Pharmacol Ther. 1980; 28(6):796-803. DOI: 10.1038/clpt.1980.237. View

10.

Gram L, Sondergaard I, Christiansen J, Petersen G, Bech P, REISBY N . Steady-state kinetics of imipramine in patients. Psychopharmacology (Berl). 1977; 54(3):255-61. DOI: 10.1007/BF00426573. View

11.

Thayssen P, Bjerre M, Kragh-Sorensen P, Moller M, Petersen O, Kristensen C . Cardiovascular effect of imipramine and nortriptyline in elderly patients. Psychopharmacology (Berl). 1981; 74(4):360-4. DOI: 10.1007/BF00432748. View

12.

REISBY N, Gram L, Bech P, Nagy A, Petersen G, Ortmann J . Imipramine: clinical effects and pharmacokinetic variability. Psychopharmacology (Berl). 1977; 54(3):263-72. DOI: 10.1007/BF00426574. View

13.

Fenimore D, Meyer C, Davis C, Hsu F, Zlatkis A . High-performance thin-layer chromatographic determination of psychopharmacologic agents in blood serum. J Chromatogr. 1977; 142:399-409. DOI: 10.1016/s0021-9673(01)92053-9. View

14.

Gram L . Plasma level monitoring of tricyclic antidepressant therapy. Clin Pharmacokinet. 1977; 2(4):237-51. DOI: 10.2165/00003088-197702040-00001. View

15.

Kragh-Sorensen P, Hansen C, Asberg M . Plasma levels of nortriptyline in the treatment of endogenous depression. Acta Psychiatr Scand. 1973; 49(4):444-56. DOI: 10.1111/j.1600-0447.1973.tb04437.x. View

16.

Nagy A, Johansson R . The demethylation of imipramine and clomipramine as apparent from their plasma kinetics. Psychopharmacology (Berl). 1977; 54(2):125-31. DOI: 10.1007/BF00426767. View

17.

Gurney C, Roth M, Garside R, Kerr T, Schapira K . Studies in the classification of affective disorders. The relationship between anxiety states and depressive illnesses. II. Br J Psychiatry. 1972; 121(561):162-6. DOI: 10.1192/bjp.121.2.162. View

18.

Bech P, Gram L, REISBY N, Rafaelsen O . The WHO Depression Scale. Relationship to the Newcastle Scales. Acta Psychiatr Scand. 1980; 62(2):140-53. DOI: 10.1111/j.1600-0447.1980.tb00601.x. View

19.

Gram L, Christiansen J, Overo K . Pharmacokinetic interaction between neuroleptics and tricyclic antidepressants in the rat. Acta Pharmacol Toxicol (Copenh). 1974; 35(3):223-32. DOI: 10.1111/j.1600-0773.1974.tb00742.x. View

20.

Nies A, Robinson D, Friedman M, Green R, Cooper T, RAVARIS C . Relationship between age and tricyclic antidepressant plasma levels. Am J Psychiatry. 1977; 134(7):790-3. DOI: 10.1176/ajp.134.7.790. View