Drugs online research references
J Clin Psychiatry. 1997 Oct;58(10):440-3.
Effect of sertraline on plasma nortriptyline levels in depressed elderly.
Solai LK, Mulsant BH, Pollock BG, Sweet RA, Rosen J, Yu K, Reynolds CF 3rd.
Mental Health Clinical Research Center for the Study of Late-Life Mood Disorders, University of Pittsburgh School of Medicine, Pa., USA.
BACKGROUND: Several serotonin selective reuptake inhibitors have been reported to be inhibitors of the cytochrome P450 2D6 (CYP2D6). Thus, they may increase the plasma level of secondary amine tricyclic antidepressants, which are predominantly metabolized through this enzyme. Except for a few case reports, no clinical data document the degree of this drug-drug interaction in elderly depressed patients. METHOD: We systematically examined this interaction by determining the change in plasma nortriptyline levels in 14 elderly depressed patients in whom sertraline was added to nortriptyline. RESULTS: After addition of 50 mg/day of sertraline, the median increase in plasma nortriptyline level over baseline was 2% (range, -26% to 117%; p = .30). In 2 patients (14%), there was an increase of 50% or more. For patients taking higher sertraline doses (N = 7; 100 or 150 mg/day), the median increase in plasma nortriptyline level over baseline was 40% (range, -12% to 239%; p = .08). CONCLUSION: Overall, a modest effect of sertraline was observed on nortriptyline metabolism in these elderly depressed patients. This is consistent with prior reports of a weak inhibition of CYP2D6 by sertraline in vitro and in young healthy volunteers. However, some patients showed a change in plasma nortriptyline level that would be considered clinically significant. Thus, careful monitoring of plasma nortriptyline levels is recommended in all patients treated with a combination of nortriptyline and sertraline.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9375595&dopt=Abstract
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J Affect Disord. 1997 Oct;46(1):59-67.
Concomitant use of selective serotonin reuptake inhibitors with other cytochrome P450 2D6 or 3A4 metabolized medications: how often does it really happen?
Gregor KJ, Way K, Young CH, James SP.
Outcomes Research, PCS Health Systems, Inc., Scottsdale, Arizona 85260, USA.
This study retrospectively examines the one-month concomitant use of cytochrome P450 2D6 or 3A4 metabolized medications in 544,309 patients who were also receiving selective serotonin reuptake inhibitors (SSRIs). Overall, 25.53% of SSRI patients experienced concomitant use with at least one of the 33 studied CYP 2D6 or 3A4 metabolized medications. Certain drugs and drug classes were more likely to be used concurrently among SSRI patients (e.g., benzodiazepines, tricyclic antidepressants, calcium channel blockers). Similarly, of the SSRI patients experiencing concomitant use, this concurrent use was twice as likely with cytochrome P450 medications metabolized by the 3A4 isoenzyme as with those metabolized by the 2D6 isoenzyme. Finally, the vast majority (80.9%) of SSRI patients experiencing concomitant use did so with one CYP 2D6 or 3A4 metabolized medication. In sum, concomitant use generally was not extensive and did not appear to be differential among the fluoxetine, paroxetine, or sertraline patient comparison groups.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9387087&dopt=Abstract
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Pharmacol Toxicol. 1997 Dec;81(6):259-64.
Interactions between promazine and antidepressants at the level of cellular distribution.
Daniel WA, Wojcikowski J.
Polish Academy of Sciences, Institute of Pharmacology, Krakow, Poland.
The pharmacokinetic interactions in clinical combinations of a phenothiazine neuroleptic and antidepressants at the level of cellular distribution were investigated. Uptake experiments were performed on slices of various rat tissues as a system with intact lysosomes. Promazine and antidepressants (imipramine, amitriptyline, sertraline, fluoxetine) were incubated separately or jointly with tissue slices for 1 hr. Initial concentration of each drug was 5 microM. The interaction studies were carried out in the absence and presence of ammonium chloride (20 mM), a lysosomotropic compound which increases the internal pH value of lysosomes. All the tissues known for their abundance of lysosomes (the lungs, liver, kidneys) were the site of an interaction between promazine and antidepressants. The neuroleptic and antidepressants mutually inhibited their tissue uptake. The potency of interference of each antidepressant with the lysosomal uptake of promazine was similar. The interactions did not occur in the presence of ammonium chloride, which indicates involvement of the lysosomal trapping. Carbamazepine, a lipophilic but non-lysosomotropic drug, did not interfere with the promazine uptake, and the adipose tissue containing very few lysosomes was never the site of interaction in our experiment. Distribution interactions were also observed in the brain and in some cases in muscles (the tissues less abundant of lysosomes), the effect of the inhibitory drug being usually more potent than that of ammonium chloride. Most of the interactions occurring in these two tissues were also observed in the presence of ammonium chloride. Most of the interactions occurring in these two tissues were also observed in the presence of ammonium chloride, which suggests involvement, at least partially, of a non-lysosomal trapping mechanism. The consequences of the observed distributive interactions at the level of lysosomal trapping in vitro are diminished intralysosomal concentration of the basic lipophilic psychotropic and its increase in cell membranes and fluids. In vivo, a shift from the organs or tissues rich in lysosomes to those less abundant in these organella, and an increase in the free drug concentration in body fluids may be expected. In conclusion, the obtained results show that, regardless of the previously known metabolic interactions between psychotropics, interactions at the levels of cellular and body distribution are also feasible.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9444666&dopt=Abstract
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