Atomoxetine EP Impurity C HCl 化学特性,用途語,生産方法
使用
p-Tolyloxy Atomoxetine Hydrochloride is an impurity of Atomoxetine Hydrochloride(A791400) which is a norepinephrine reuptake inhibitor.
薬物動態学
Atomoxetine is well absorbed from the GItract and cleared primarily by metabolism, with the majority of the
dose being excreted into the urine. Atomoxetine is metabolized primarily by CYP2D6 to its major active
metabolite, 4-hydroxyatomoxetine, which is eliminated as its glucuronide. Peak plasma
concentrations of atomoxetine occur 1 to 2 hours after oral administration. Significant differences are seen in
the elimination half-life between normal metabolizers, extensive metabolizers, and poor metabolizers. Atomoxetine exhibited an elimination half-life of 3 to 6 hours for normal and extensive metabolizers and
17 to 21 hours for poor metabolizers. CYP2C19 is the other enzyme primarily responsible for the
formation of its minor metabolite N-desmethylatomoxetine.
臨床応用
Atomoxetine is used as a safe and well-tolerated “nonstimulant” treatment of ADHD in both adults and
children and of depression. Among children and adolescents aged 8 to 18 years, atomoxetine was superior to
placebo in reducing symptoms of ADHD and in improving social and family functioning symptoms. Oral
atomoxetine is promoted as an alternative to conventional ADHD therapy with methylphenidate,
dextroamphetamine, and pemoline. It also can be a replacement for bupropion or for TCAs. Onset of action is
approximately 7 days.
副作用
At therapeutic doses, no serious drug-related adverse effects have been encountered. Adverse effects have
included modest increases in diastolic blood pressure and heart rate, anorexia, weight loss, somnolence,
dizziness, GI effects (nausea), dry mouth, and skin rash.
酵素阻害剤
This ADHD drug (FWfree-base = 255.36 g/mol; FWhydrochloride = 291.81 g/mol;
CAS 83015-26-3), also known as LY139603, Strattera?, and systematically
as (3R) -N-methyl-3- (2-methylphenoxy) -3-phenylpropan-1-amine; (R) -N-
methyl-3-phenyl-3- (o-tolyloxy) -propan-1-amine, potently inhibits the
presynaptic norepinephrine transporter, Ki = 4.5 nM and is used to
treat depression and attention-deficit/hyperactivity disorder. In 2002,
Strattera became the first FDA-approved nonstimulant for the treatment of
ADHD. The mechanism of action is related to its selective inhibition of
presynaptic norepinephrine reuptake in the prefrontal cortex.
Atomoxetine demonstrates high affinity and selectivity for norepinephrine
transporters, but little or no affinity for neurotransmitter receptors.
Atomoxetine demonstrates preferential binding to areas of known high
distribution of noradrenergic neurons, such as the fronto-cortical
subsystem. Atomoxetine undergoes extensive biotransformation, which is
affected by poor metabolism by cytochrome P450 (CYP2D6) in a small
percentage of the population. (Note: Atomoxetine was originally named
tomoxetine, but was changed to avoid any potential confusion with
tamoxifen.) Key Pharmacokinetic Parameters: See Appendix II in Goodman
& Gilman’s THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, 12th Edition
(Brunton, Chabner & Knollmann, eds.) McGraw-Hill Medical, New York.
Atomoxetine EP Impurity C HCl 上流と下流の製品情報
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