Effect of Sertraline on Protein Binding of Warfarin
- 1 January 1997
- journal article
- clinical trial
- Published by Springer Nature in Clinical Pharmacokinetics
- Vol. 32 (Supplement) , 37-42
- https://doi.org/10.2165/00003088-199700321-00006
Abstract
The effect of sertraline on the plasma protein binding of warfarin was investigated in a nonblinded randomised placebo-controlled parallel trial in 12 healthy male volunteers. The study participants received single doses of warfarin before administration of sertraline or placebo and again after sertraline or placebo had been administered for 22 days. Treatment with sertraline for 26 days increased the area under the mean prothrombin time vs time curve by 145 sec · h (7.9%), compared with a decrease of 17 sec · h (−1.0%) in the placebo group. Although statistically significant (p=0.02), this difference was not felt to be clinically meaningful. There appeared to be a slight delay in the normalisation of the prothrombin time in the sertraline-treated group after the second dose of warfarin, which also would not be expected to be clinically significant. After 22 days, a statistically significant (p=0.02) increase in unbound warfarin was observed in the sertraline group compared with the placebo-treated individuals. Neither the change in prothrombin time nor the change in plasma protein binding were considered to have any clinical relevance; however, good clinical practice dictates that prothrombin time should be monitored in patients treated concurrently with warfarin and sertraline to ensure that the integrity of coagulation response is maintained. The metabolism of warfarin is principally mediated by the cytochrome P450 (CYP) isoenzyme CYP2C9/10. Thus, sertraline appears to have a minimal effect on the CYP2C9/10 isoenzyme.Keywords
This publication has 18 references indexed in Scilit:
- A Study of the Potential Effect of Sertraline on the Pharmacokinetics and Protein Binding of TolbutamideClinical Pharmacokinetics, 1997
- Sertraline 50 mg daily: the optimal dose in the treatment of depressionInternational Clinical Psychopharmacology, 1995
- Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the etiology of (S)-warfarin-drug interactionsChemical Research in Toxicology, 1992
- Use of a Human Serum Albumin-Based High-Performance Liquid Chromatography Chiral Stationary Phase for the Investigation of Protein Binding: Detection of the Allosteric Interaction between Warfarin and Benzodiazepine Binding SitesJournal of Pharmaceutical Sciences, 1991
- Evaluation of the potential for interactions of paroxetine with diazepam, cimetidine, warfarin, and digoxinActa Psychiatrica Scandinavica, 1989
- FluvoxamineDrugs, 1986
- Factors Affecting the Measurement of Lidocaine Protein Binding by Equilibrium Dialysis in Human SerumJournal of Pharmaceutical Sciences, 1985
- Drug Interactions with WarfarinDrugs, 1983
- Clinical Pharmacokinetics of Oral AnticoagulantsClinical Pharmacokinetics, 1979
- Warfarin metabolism in man: identification of metabolites in urineJournal of Clinical Investigation, 1970