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Psychopharmacology

, Volume 54, Issue 3, pp 255–261 | Cite as

Steady-state kinetics of imipramine in patients

  • Lars F. Gram
  • Ib Søndergaard
  • Johannes Christiansen
  • Gorm Odden Petersen
  • Per Bech
  • Niels Reisby
  • Ilse Ibsen
  • Jørgen Ortmann
  • Adam Nagy
  • Sven J. Dencker
  • Ove Jacobsen
  • Ole Krautwald
Original Investigations

Abstract

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 μg/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 μg/l, DMI: 24–659 μg/l and IP+DMI: 58–809 μg/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.

Key words

Imipramine Desipramine Steady-state levels Individual variation Age differences Hepatic elimination Protein binding Logarithmic transformation 

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Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • Lars F. Gram
    • 1
  • Ib Søndergaard
    • 1
  • Johannes Christiansen
    • 2
  • Gorm Odden Petersen
    • 3
  • Per Bech
    • 3
  • Niels Reisby
    • 4
  • Ilse Ibsen
    • 4
  • Jørgen Ortmann
    • 4
  • Adam Nagy
    • 5
    • 6
  • Sven J. Dencker
    • 5
    • 6
  • Ove Jacobsen
    • 7
  • Ole Krautwald
    • 7
  1. 1.Department of PharmacologyUniversity of CopenhagenDenmark
  2. 2.Department of Clinical Chemistry A, RigshospitaletUniversity of CopenhagenDenmark
  3. 3.Department of Psychiatry, RigshospitaletUniversity of CopenhagenDenmark
  4. 4.Department of PsychiatryMunicipal HospitalCopenhagenDenmark
  5. 5.Department IILillhagen HospitalGothenburgSweden
  6. 6.Department of Clinical ChemistrySahlgren's HospitalGothenburgSweden
  7. 7.Department PState Mental HospitalGlostrupDenmark

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