Drugs online research references
Clin Nephrol. 1995 Aug;44(2):121-4.
Hemodialyzability of sertraline.
Schwenk MH, Verga MA, Wagner JD.
St. John's University, College of Pharmacy and Allied Health Professions, Department of Clinical Pharmacy Practice, Jamaica, New York 11439, USA.
Sertraline is an antidepressant which selectively inhibits the neuronal uptake of serotonin in the central nervous system. The pharmacokinetics of sertraline in end-stage renal disease (ESRD) and the effect of hemodialysis on sertraline clearance is unknown. A dose of 100 mg sertraline was administered to two anuric hemodialysis patients after hemodialysis. During the next hemodialysis session, simultaneous pre- and post dialyzer blood samples were obtained at the start of and hourly throughout dialysis until completion. All spent dialysate was collected hourly, quantified and an aliquot retained. Additional blood samples were obtained approximately 20 hours after dialysis and prior to the next treatment. Serum and dialysate were assayed for sertraline by gas chromatography-mass spectroscopy. Initial sertraline serum concentrations were similar to those observed in subjects with normal renal function given the same sertraline dose, implying unaltered absorption and distribution. Sertraline was not detected in any dialysate sample. The elimination half-life was 42-92 h (normally 24-36 h), suggesting impaired clearance. Smaller doses of sertraline may be required in ESRD patients, yet post-hemodialysis supplementation is unnecessary.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8529300&dopt=Abstract
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J Pharmacol Exp Ther. 1995 Dec;275(3):1131-5.
Effect of fluoxetine, norfluoxetine, sertraline and desmethyl sertraline on human CYP3A catalyzed 1'-hydroxy midazolam formation in vitro.
Ring BJ, Binkley SN, Roskos L, Wrighton SA.
Department of Drug Metabolism and Disposition, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
The ability of fluoxetine, norfluoxetine, sertraline and desmethyl sertraline to inhibit the CYP3A subfamily of cytochromes P450 was examined in vitro, using the formation of 1'-hydroxy midazolam as a probe for CYP3A catalytic activity. The inhibition observed with these four compounds was modeled using competitive, noncompetitive, uncompetitive and mixed competitive/noncompetitive relationships by nonlinear regression analysis. The best fit model of the inhibition of CYP3A-mediated 1'-hydroxy midazolam formation by all four compounds examined was determined to be mixed inhibition. The calculated Ki values were 65.7 +/- 12.0 microM for fluoxetine, 19.1 +/- 1.9 microM for norfluoxetine, 64.4 +/- 11.6 microM for sertraline and 48.1 +/- 11.6 microM for desmethyl sertraline. Steady-state plasma levels of fluoxetine and norfluoxetine can approach a concentration of 1 microM (approximately 350 ng/ml of plasma). Assuming an inhibitor concentration of 1 microM and a concentration of the substrate substantially below its Km (at least 10-fold lower), the results reported predict that fluoxetine and norfluoxetine together would inhibit CYP3A catalytic activity by less than 7% (less than 0.7% if the unbound plasma concentration of fluoxetine is considered). By using the same assumptions and concentrations for sertraline and desmethyl sertraline, these agents together would be predicted to inhibit the metabolic clearance of a coadministered CYP3A metabolized drug by less than 4%. The observations reported here suggest that fluoxetine and sertraline would have little effect on CYP3A-mediated clearance of coadministered drugs.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8531073&dopt=Abstract
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J Clin Psychol. 1999 Jan;55(1):129-33.
Trends in the use of selective serotonin reuptake inhibitors in nine Department of Veterans Affairs outpatient facilities.
Voris JC.
University of South Carolina, College of Pharmacy, Dorn Veterans Hospital, Columbia 29209-1639, USA.
The average daily dose and need for dose escalations for the drugs known as selective serotonin reuptake inhibitors (SSRIs) has frequently been a point of controversy. This study reports on the information gathered from nine Veterans Affairs hospitals over a two six-month periods. Average daily doses of fluoxetine, paroxetine, and sertraline started at 30.9 mg, 24.2 mg, and 87.8 mg and ended at 28.4 mg, 24.2 mg, and 89.8 mg, respectively. Cost, number of prescriptions, and dosage strength data is also presented.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10100839&dopt=Abstract
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