Pharmacokinetic interaction study of citalopram and cimetidine in healthy subjects

  title={Pharmacokinetic interaction study of citalopram and cimetidine in healthy subjects},
  author={Morten Priskorn and Frank Larsen and A. Segonzac and M. Moulin},
  journal={European Journal of Clinical Pharmacology},
Citalopram is an antidepressant belonging to a class of drugs that selectively and potently inhibits serotonin reuptake into central neurones [1]. Cimetidine inhibits the activity of the cytochrome P450 enzyme system [2], in particular the CYP2D6, CYP3A4 and CYP1A2 isozymes [3]. Demethylation of citalopram to form demethylcitalopram (DCT) appears to be mediated via CYP2C19, while the further demethylation of DCT to form didemethylcitalopram (DDCT) appears to a large extent to be mediated via… 

Steady-state pharmacokinetics of the enantiomers of citalopram and its metabolites in humans.

A modest, but statistically significant, stereoselectivity in the disposition of citalopram and its two main metabolites was observed, apparently more related to clearance, rather than to distributional mechanisms.

Pharmacokinetics of selective serotonin reuptake inhibitors.

Single-dose pharmacokinetics of citalopram in patients with moderate renal insufficiency or hepatic cirrhosis compared with healthy subjects

No reduction of citalopram dosage is warranted in patients with moderately impaired renal function, however, that may not apply for patients with severe renal failure, and in Patients with impaired hepatic function, prescription of a lower dosage of cITALopram may be appropriate.

Studies on the Stereoselective Metabolism of Citalopram by Human Liver Microsomes and cDNA-Expressed Cytochrome P450 Enzymes

Using human mixed liver microsomes and cDNA-expressed CYP enzymes, it is confirmed that CYP3A4, 2C19 and 2D6 are involved in the first demethylation step of citalopram, all favouring conversion of the biologically active S-enantiomer.

The effect of cimetidine or omeprazole on the pharmacokinetics of escitalopram in healthy subjects.

In view of the good tolerability of escitalopram, the pharmacokinetic changes observed on co-administration with cimetidine or omeprazole are unlikely to be of clinical concern.

Citalopram and cardiac toxicity

Citalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant that is widely used in clinical practice. Recent data have indicated that high therapeutic citalopram doses may cause

Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-citalopram.

S-CT, biotransformed by three CYP isoforms in parallel, is unlikely to be affected by drug interactions or genetic polymorphisms and are also unlikely to cause clinically important drug interactions via CYP inhibition.

Pharmacokinetic-pharmacodynamic modelling of QT interval prolongation following citalopram overdoses.

Administration of activated charcoal was shown to reduce the risk that the QT interval exceeds a previously defined threshold and therefore is expected to cut the risk of torsade de pointes (TdP) in patients with citalopram overdose.



Pharmacokinetics of Citalopram in Relation to the Sparteine and the Mephenytoin Oxidation Polymorphisms

It was shown that the citalopram elimination partially depends on the mephenytoin oxygenase, since steady-state serum concentration, half-life, and area under the serum concentration/time curve for cITALopram were significantly higher in poor metabolizers of mephenYtoin than in extensive metabolizer of me Pheny toin.

Effect of cimetidine on renal and hepatic drug elimination: Studies with triamterene

There was a reduced recovery of triamterene and its metabolites in urine after Cimetidine, suggesting a decreased absorption, and results are consistent withCimetidine inhibiting cytochrome P‐450 enzymes in the liver and also competing with triamTerene for renal tubular secretion.

Pharmacokinetic Interactions of Cimetidine 1987

Cimetidine reduces the renal clearance of drugs which are organic cations, by competing for active tubular secretion in the proximal tubule of the kidney, reducing the renal clearances of procainamide, ranitidine, triamterene, metformin, flecainide and the active metabolite N-acetylprocainamide.

Pharmacological characterization of selective serotonin reuptake inhibitors (SSRIs)

  • J. Hyttel
  • Psychology, Biology
    International clinical psychopharmacology
  • 1994
Since the marketed SSRIs all show clear antidepressant effect, this receptor regulation seems not to be a prerequisite for clinical antidepressant activity.

Reduction of metformin renal tubular secretion by cimetidine in man.

It is concluded that cimetidine inhibits the renal tubular secretion of met formin in man, resulting in higher circulating plasma concentrations, and the dose of metformin should be reduced when cimeidine is co-prescribed.

The pharmacokinetics of citalopram

  • Rev Contemp Pharmacother
  • 1995

Di€erential inhibition of individual liver cytochromes P-450 by cimetidine

  • Gastroenterology
  • 1991