Fluoxetine Research Paper

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Fluoxetine is also known as Prozac, common antidepressant drug (1). It works as selective, competitive reversible antagonist of serotonin receptor that prevent reuptake of serotonin from synapse (2). Due to selectivity, little effect on other neurotransmitters, such as dopamine and noradrenaline. It increase the concentration of serotonin at the synapse and serotonergic neuronal transmission strength, and it triggers negative feedback loop of serotonin, which reduce the conversion of tryptophan to serotonin (3). Fluoxetine does not display species difference, but effect as antidepressant is depend on the dose thought out number of studies. Fluoxetine is administrated as tablets with usual starting dose of fluoxetine is 20mg per day, and it…show more content…
It is metabolised by different subtypes of CYP450 enzymes, and converted to active metabolites, n-demethylation metabolite (norfluoxetine). Both fluoxetine and norfluoxetine converted to p-trifluoromethylphenol by o-dealkylation, and to hippuric acid for excretion (3). The elimination half-life of fluoxetine for single dose is one to four days, for multiple doses is four to six days; half-life of norfluoxetine is seven to ten days (5). As well as the serotonin receptor, it also interact with channel ions (Na+, K+, and Ca2+), and monoamine oxidases A and B (6). Both fluoxetine and norfluoxetine show highest tissue concentration in lung, moderate in brain, heart, kidney, and liver, and low in embryonic/fetal tissue, amniotic fluid, and maternal plasma of rat (7,…show more content…
It is also known to cause drug interaction in dose dependence manner, single and multiple dose of 30mg did not affect the elimination or area under the curve (AUC) of diazepam 10mg, tolbutamide 1000mg or chlorothiazide 500mg, or of secobarbitone (secobarbital) 150mg, but 60mg prolonged the elimination of diazepam, but physiological responses to diazepam were unaffected (3). Also, fluoxetine might have enhanced the toxic effects of other drugs, such as, cocaine because of its weak pro-arrhythmogenic properties (10). Therefore, the concentration of fluoxetine and norfluoxetine is important.
The concentration could be altered due to level and activation of CYP450. Fluoxetine is substrate of CYP2D6 and CYP2C9, and potent inhibitor of CYP2D6, and moderate inhibitor of CYP2C9, 2C19, and 3A4 (11). One study shows genetic predisposition is mostly due to CYP2C9 (12). Another case report shows fluoxetine related death of a child with defect at CYP2D6 gene locus on chromosome 22 (poor metaboliser), due to high level of fluoxetine along with other drugs (methylphenidate, promethazine, and clonidine)
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