Drugs online research references
Pharmacol Toxicol. 1997 Feb;80(2):62-8.
Contribution of lysosomal trapping to the total tissue uptake of psychotropic drugs.
Daniel WA, Wojcikowski J.
Polish Academy of Sciences, Institute of Pharmacology, Krakow, Poland.
The present study was aimed at assessing individual contributions of the phospholipid binding and lysosomal trapping to the total tissue uptake of psychotropic drugs with different chemical structures, such as promazine, imipramine, amitriptyline, fluoxetine, sertraline (basic lipophilic drugs) and carbamazepine (lipophilic, but not basic). We also tried to find out whether lysosomal trapping may be involved in the pharmacokinetic interactions in clinical combinations of psychotropics. Uptake experiments were carried out on slices of various rat tissues as a system with intact lysosomes. Initial concentration of each drug was 5 microM. The results were compared with those obtained in the presence of the "lysosomal inhibitors", ammonium chloride or monensin. The basic lipophilic psychotropics showed high uptake in tissues known for the abundance of lysosomes, mainly the lungs. The highest drug accumulation was found for promazine and amitriptyline. "Lysosomal inhibitors" significantly decreased the uptake of the basic lipophilic drugs, particularly in the lungs and liver. The most potent effect was observed for amitriptyline, imipramine and promazine. The brain showed moderate accumulation of basic lipophilic psychotropics and the effect of the "lysosomal inhibitors" was significant only in the case of amitriptyline, imipramine and sertraline. The only exception to the above regularity were imipramine and sertraline which were taken up more extensively by the adipose tissue than by lysosome-rich tissues such as the lungs or liver. Carbamazepine did not show lysosomotropism. Amitriptyline and promazine mutually decreased their uptake by lung slices when the drugs were incubated jointly. In the presence of ammonium chloride the interaction did not occur. In conclusion, the obtained results show that (1) the lysosomal trapping is an important factor determining the distribution of the basic lipophilic psychotropics; however (2) their tissue uptake depends more on the phospholipid binding than on the lysosomal trapping; (3) the lysosomal trapping may be involved in the pharmacokinetic interactions between psychotropics.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9060036&dopt=Abstract
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J Endocrinol Invest. 1996 Dec;19(11):727-33.
Sertraline enhances the effects of cognitive-behavioral treatment on weight reduction of obese patients.
Ricca V, Mannucci E, Di Bernardo M, Rizzello SM, Cabras PL, Rotella CM.
Dipartimento di Scienze Neurologiche e Psichiatriche, Universita di Firenze, Italy.
Serotonin reuptake inhibitors, such as dexfenfluramine, fluoxetine and fluvoxamine, have been proposed as therapeutical tools for the treatment of eating disorders and obesity. Sertraline, a SSRI used in the treatment of depression, interferes with eating behavior in animal models, but it has not been tested in obese humans. Aim of this study is the assessment of the effects of sertraline on eating attitudes and body weight in obese patients with and without mood disorders. A consecutive series of 65 obese out-patients aged 18-65 years, with a body mass index (BMI) > 30 kg/m2, was treated for 6 months with sertraline 150 mg/day per os, in addition to a cognitive-behavioral treatment (CBT). A consecutive series of 60 obese patients with similar characteristics, who were treated with CBT only, were used as control group. A greater reduction of BMI (mean +/- SD) was observed in sertraline-treated patients when compared to controls (from 35.3 +/- 5.7 to 32.0 +/- 5.4 kg/m2 in sertraline-treated patients, from 37.1 +/- 7.0 to 36.0 +/- 7.1 kg/m2 in controls; 6.5 +/- 5.4% vs. 3.0 +/- 6.3%; p < 0.01), while a similar change in eating attitudes (evaluated through the BITE questionnaire) was observed in both groups. Effects of sertraline on eating attitude and body weight were similar in patients with and without mood disorders. In conclusion, sertraline, administered together with CBT, seems to be more effective in inducing weight loss in obese patients when compared with CBT alone, and therefore it could be a useful tool in the first months of CBT for severe obesity.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9061505&dopt=Abstract
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Clin Pharmacokinet. 1997;32 Suppl 1:22-30.
Pharmacokinetics of sertraline and its N-demethyl metabolite in elderly and young male and female volunteers.
Ronfeld RA, Tremaine LM, Wilner KD.
Pfizer Central Research, Groton, Connecticut, USA.
A nonblinded study was conducted to compare the pharmacokinetic properties of the selective serotonin reuptake inhibitor sertraline in 22 young (aged 18 to 45 years) and 22 elderly (> 65 years) volunteers, of whom half were male and half were female. In this study, sertraline was administered at a dosage of 200mg once daily (the maximum recommended daily dosage) for 21 days after upward dosage titration from 50 mg/day over a 9-day period. Thus, this study was designed to measure the effect of age and gender on the pharmacokinetic properties of sertraline at the maximum dosage recommended for clinical use. The terminal elimination half-life (t1/2 beta ) of sertraline was similar in young females, elderly males and elderly females (mean t1/2 beta ranged from 32.1 to 36.7 hours in these groups) but shorter (22.4 hours) in the young males. The mean maximum plasma sertraline concentration (Cmax) and the mean steady-state area under the plasma concentration-time curve from time zero to 24 hours postdose (AUC24) were also similar between the young females, elderly males and elderly females, but were approximately 25% lower in the young males. The time to Cmax was unaffected by age or gender and ranged from 6.4 to 6.9 hours. N-Demethylsertraline is the principal metabolite of sertraline and does not contribute significantly to its serotonergic actions. The mean values for N-demethylsertraline trough plasma concentrations, AUC24 and Cmax were comparable in elderly males and females and young females but lower in young males. The ratios of mean AUC24 and Cmax for N-demethylsertraline to the AUC24 and Cmax for sertraline were similar between the 4 groups.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9068932&dopt=Abstract
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