Drugs online research references
Clin Chem. 1989 Mar;35(3):453-6.
Automated determination of drugs in serum by column-switching high-performance liquid chromatography. IV. Separation of tricyclic and tetracyclic antidepressants and their metabolites.
Matsumoto K, Kanba S, Kubo H, Yagi G, Iri H, Yuki H.
Clinical Chemistry, School of Pharmaceutical Sciences, Toho University, Chiba, Japan.
We describe automated column-switching high-performance liquid chromatography for determining nine tricyclic and tetracyclic antidepressants (TCAs) and their metabolites in human serum. TSKgel ODS-80TM and TSKprecolumn PW (Tosoh Co., Tokyo) are used in the analytical column and the precolumn, respectively. A 200-microL serum sample is directly injected onto the precolumn. After washing the serum proteins from the precolumn with potassium phosphate buffer, the precolumn connection is switched to introduce the retained substances onto the analytical column. The drugs are then eluted within 30 min with an acetonitrile/potassium phosphate buffer mixture containing sodium 1-heptanesulfonate. The analytical recoveries (95-104%), reproducibilities (within-run CV less than 3%), and detection limits (10 micrograms/L) indicate that this HPLC system is suited for therapeutic drug monitoring. Correlations were good between the TCA concentrations in serum and administered dose (r = 0.713, n = 41), and between 10-hydroxynortriptyline and nortriptyline in serum (r = 0.691, n = 24).
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2920412&dopt=Abstract
Psychopharmacology (Berl). 1982;76(3):236-9.
Do urinary MHPG and plasma drug levels correlate with response to amitriptyline therapy?
Gaertner HJ, Kreuter F, Scharek G, Wiatr G, Breyer-Pfaff U.
Twenty-nine inpatients with primary affective disorder were treated with 150 mg amitriptyline (AT) daily for 28 days. Pretreatment urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured in two or three 24-h urine samples. Plasma levels of AT and nortriptyline (NT) were determined after 14, 21, and 28 days of treatment. MHPG excretion was significantly correlated with clinical response to treatment. Responders defined by two different methods showed higher pretreatment MHPG excretion than nonresponders. Correspondingly, high MHPG excretors (median split) showed significantly more improvement than low excretors. These relationships were even more apparent when possibly incomplete urine samples (creatinine excretion below 1000 mg/24h) were excluded. The high and low MHPG subgroups did not significantly differ from each other in their plasma levels of AT, NT, or AT plus NT. A significant rank correlation between clinical response and plasma levels of AT and/or NT did not exist, but there was a trend towards lower levels in responders.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6808543&dopt=Abstract
Psychopharmacology (Berl). 1986;90(3):384-9.
Platelets and biogenic amines. 2. Indications for a discrete low affinity uptake mechanism shared by norepinephrine and 5-hydroxytryptamine in human platelets.
Malmgren R.
The uptake of norepinephrine (NE) by human platelets at 10(-9)-5 X 10(-4) M of labelled amine concentration was investigated. At physiological concentrations of NE the uptake was unsaturable and could not be inhibited by imipramine or ouabain. At NE concentrations between 25 and 485 microM the uptake also comprised a saturable component that could be completely blocked by imipramine and partly by ouabain. The saturable uptake of NE had an apparent Km of 273 +/- 50 microM and a Vmax of 0.19 +/- 0.05 pmole/10(6) platelets/min. The affinity of NE (IC50) for the 5-HT transporting carrier was 2.3 mM, 8.4 times higher than the apparent Km for saturable NE uptake. The affinity of 5-HT (IC50) for the NE-transporting carrier was 5.8 microM, 5.8 times higher than the apparent Km for saturable 5-HT transport. Imipramine and norzimeldin were equipotent inhibitors of saturable NE uptake, the potency being of the same degree as that for saturable 5-HT uptake. The tertiary amine amitriptyline was 6 times more effective in inhibiting saturable NE uptake than its demethylated product nortriptyline. Nortriptyline and its hydroxylated E- and Z-isomers had a stronger inhibitory effect on saturable NE uptake than on uptake of 5-HT. The results suggest that human platelets possess two separate amine-transporting carriers, both having their highest affinity for 5-HT. The one with the lowest affinity for 5-HT can also accept NE as a substrate. The human platelet does not possess a high-affinity uptake system for NE comparable to that in adrenergic tissue.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3097728&dopt=Abstract
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