Clinical Pharmacokinetics of Imipramine and Desipramine

  title={Clinical Pharmacokinetics of Imipramine and Desipramine},
  author={Floyd R. Sallee and B. G. Pollock},
  journal={Clinical Pharmacokinetics},
  • F. Sallee, B. Pollock
  • Published 1 May 1990
  • Medicine, Biology, Psychology
  • Clinical Pharmacokinetics
SummaryThe pharmacokinetics of Imipramine and desipramine have been extensively investigated with recent studies designed to understand sources of intersubject variability and to study discrete clinical populations rather than healthy volunteers. Sources of intersubject variability in pharmacokinetics are both genetic (oxidative phenotype) and environmental. Oxidative phenotype has an important impact on first-pass metabolism. In individuals with poor metabolism, systemic availability for… 
Clinical Pharmacokinetics of Clomipramine
Clomipramine, like the other tricyclics, is an antidepressant with a fairly narrow therapeutic range, combined with a high interindividual variability, makes this class of drugs ideal candidates for blood concentration monitoring.
Desipramine, substrate for CYP2D6 activity: population pharmacokinetic model and design elements of drug-drug interaction trials.
The semi-mechanistic population model developed is suitable to describe the pharmacokinetic behaviour of desipramine for the dose routinely used in drug-drug interaction (DDI) studies and a sample size of 21 subjects in cross-over design is appropriate for assessing CYP2D6 interaction with novel compounds.
Steady-state plasma concentrations of imipramine and desipramine in relation to S-mephenytoin 4'-hydroxylation status in Japanese depressive patients.
The individually predetermined assessment of the CYP2C19-mediated metabolic capacity of imipramine would be more valuable than that of the CyP2D6-mediated capacity for forecasting the steady-state concentrations of im ipramine and desipramines in Japanese depressive patients, thereby attaining an individualized optimization of imIPramine therapy.
The Use of In Vitro Data and Physiologically-Based Pharmacokinetic Modeling to Predict Drug Metabolite Exposure: Desipramine Exposure in Cytochrome P4502D6 Extensive and Poor Metabolizers Following Administration of Imipramine
This example suggested that mechanistic PBPK modeling combined with information obtained from in vitro studies can provide quantitative solutions to predict in vivo pharmacokinetics of drugs and major metabolites in a target human population.
Imipramine and 2-hydroxyimipramine: comparative cardiotoxicity and pharmacokinetics in swine
It is concluded that 2-OH-IMI has increased penetrance into the CNS despite a smaller Vd and that it is significantly more cardiotoxic than its parent.
Effect of Terbinafine on the Pharmacokinetics and Pharmacodynamics of Desipramine in Healthy Volunteers Identified as Cytochrome P450 2D6 (CYP2D6) Extensive Metabolizers
Terbinafine‐CYP2D6 inhibition was evaluated by assessing 48‐hour concentration‐time profiles of the tricyclic antidepressant desipramine in 12 healthy volunteers identified as extensive cytochrome
Development and Qualification of Physiologically Based Pharmacokinetic Models for Drugs With Atypical Distribution Behavior: A Desipramine Case Study
A physiologically based pharmacokinetic (PBPK) model is developed and qualified for desipramine, which accounts for the high Vss of the drug following intravenous and oral administration of doses up to 100 mg and the extended time to reach maximum concentration after oral dosing due to enterocyte trapping.
The Effects of Desvenlafaxine and Paroxetine on the Pharmacokinetics of the Cytochrome P450 2D6 Substrate Desipramine in Healthy Adults
Desvenlafaxine, especially at the recommended therapeutic dose of 50 mg/d for major depressive disorder in the United States, has little potential to interact with CYP2D6 substrates.
Pharmacokinetics of the newer antidepressants: clinical relevance.
  • C. DeVane
  • Medicine, Biology
    The American journal of medicine
  • 1994


Multiple-dose pharmacokinetics of imipramine and its major active and conjugated metabolites in depressed patients.
The data indicate accumulation of substantial serum concentrations of glucuronide conjugates after therapeutic doses of IMI in depressed patients and similarities within patients in disposition of metabolite pairs.
Active metabolites of imipramine and desipramine in man
On the basis of a steady‐state OH‐DMI/DMI ratio of <1/30 in plasma 5% of the population studied could be classified as deficient DMI hydroxylators, the same as the incidence of deficient debrisoquine hydroxyators reported in other populations.
Plasma Concentration Monitoring of Hydroxylated Metabolites of Imipramine and Desipramine
Variable metabolite concentrations and the uncertainty of their relative psychoactivity may contribute to the difficulties in relating antidepressant efficacy to serum concentrations of the administered IMI or DMI.
Pharmacokinetic factors affecting antidepressant drug clearance and clinical effect: evaluation of doxepin and imipramine--new data and review.
At doses approaching the upper range recommended for the treatment of depression, Cpss appear to approach, in at least a few individuals, the maximum metabolic capacity of the patient, leading to greater-than-expected increases in concentrations for a given dosage increment.
Nonlinear desipramine kinetics: Prevalence and importance
Plasma desipramine concentrations increased significantly more than that predicted by the dose increase; however, only one third of the sample had substantial nonlinear changes (an increase in the concentration 50% greater than expected).
Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers
The findings suggest that recently detoxified alcoholics may require higher doses of imipramine than do nonalcoholic subjects and that periodic monitoring of plasma levels may be required for recently abstinent alcoholics treated with antidepressants.
Imipramine and desipramine disposition in the elderly.
Kinetic variables for the respective drugs were determined from multiple plasma drug concentrations from samples obtained during 96 hr after the dosage, and indicated no difference in absolute bioavailability between the elderly and young of either sex.
The nonlinear kinetics of desipramine and 2‐hydroxydesipramine in plasma
Levels of OH‐D rose in proportion to dose, suggesting that saturation of DMI elimination by 2‐hydroxylation could not explain DMI plasma level changes, and there were no dose‐dependent effects on the disposition of amitriptyline or its metabolite nortriptylines in subjects receiving the same amitripyline dose.
Hydroxydesipramine in the elderly.
The findings of elevated hydroxy levels in the elderly are consistent with prior reports, but the clinical importance of an 11 ng/ml difference, particularly in relation to total drug levels averaging 220 ng/ML, is questioned.