Fluoxetine half-life

In a recent study, Walters et al. [141] described the occurrence and loss of several PhC from biosolid-soil mixtures exposed at ambient outdoor conditions for 3 years. Some compounds showed no detectable loss over the monitoring period, including diphenhydramine, fluoxetine, thiabendazole and triclosan, while half-life estimates ranging from 182 to 3,466 days were determined for others such as azithromycin, carbamazepine, ciprofloxacin, doxycycline, tetracycline, 4-epitetracycline, gemfibrozil, norfloxacin and triclosan. These findings highlight the potential use of T. versicolor to reduce the impact of biosolids once released to the environment, which could reduce the concentrations of PhC in much shorter periods of treatment. 

Fluoxetine Alprazolam Increased plasma concentrations and half-life of alprazolam increased psychomotor impairment... 

SSRI structurally related to fluoxetine with a shorter half-life, was reported to be an effective and generally well-tolerated treatment for men with moderate-to-severe PE in clinical trial [13,14],... 

Changing a patient from one MAOI to another, or to a TCA, requires a "wash-out" period of at least 2 weeks to avoid the possibility of a drug interaction. There is evidence to suggest that a combination of an MAOI with clomipramine is more likely to produce serious adverse effects than occurs with other TCAs. Regarding the newer non-tricyclic antidepressants, it is recommended that a "wash-out" period of at least 5 weeks be given before a patient on fluoxetine is given an MAOI this is due to the very long half-life of the main fluoxetine metabolite norfluoxetine. 

Fluoxetine 10 10-50 Nor Long half-life, increased plasma levels... 

Venlafaxine, although its re-uptake inhibitory activity is not restricted to serotonin, is often classified as an SSRI because of its similar spectrum of adverse reactions. It has a short elimination half-life in contrast to the other serotonin re-uptake inhibitors. Fluoxetine, norfluoxetine and paroxetine are inhibitors of their own metabolism by CYP2D6 resulting in non-linear pharmacokinetic behavior. 

Daily fluoxetine (Prozac) Long half-life of drug and risk of producing excessive CNS stimulation, sleep disturbances, and increasing agitation. Safer alternatives exist. High... 

The presence of an active metabolite and the duration of parent compound and metabolite half-life all impact the clinical interpretation of dosing, side effects, and potential for withdrawal. Fluoxetine and its active metabolite, both of which have a relatively long half-life, remain in the system for a long time after discontinuation. Industry prescribing instructions for fluvoxamine recommend a bid dosing regimen, in part because of the absence of an active metabolite. Paroxetine, without an active metabolite and with a relatively short half-life, has been anecdotally associated with late-day withdrawal effects. 

Autoinhibition The inhibition or saturation of the highest affinity enzymes responsible for the biotransformation of a drug by the drug itself, such that lower affinity enzymes become important in elimination and the half-life increases with chronic exposure to the drug (e.g., fluoxetine, paroxetine). 

Venlafaxine is dependent on CYP 2D6 and 3A3/4 enzymes for its biotransformation and eventual clearance ( 138, 139 and 140). CYP 2D6 converts venlafaxine into 0-desmethylvenlafaxine (ODV), which is believed to have pharmacological activity comparable with the parent drug based on in vitro studies (141). Thus, this metabolite is to venlafaxine as norfluoxetine is to fluoxetine in that the half-life of ODV is longer than that of the parent drug, although it is only 12 hours versus 14 days for norfluoxetine. 

The need for dose adjustment presents a special problem for fluoxetine, because of the extended half-life of its active metabolite, norfluoxetine (i.e., 7 to... 

As mentioned previously, beyond the unusually long half-life of fluoxetine and norfluoxetine, the other clinically meaningful distinction between the SSRIs is whether they produce substantial inhibition of specific CYP enzyme (Table 7-29). Fluvoxamine, fluoxetine, and paroxetine do, whereas citalopram and sertraline do not. As mentioned earlier, it is doubtful that the first three would be developed or approved for today s market because of their effects on CYP enzymes, which can cause serious and even fatal drug-drug interactions. 

The clinician must also be aware of the long half-life (several days) of fluoxetine because the potential for this reaction remains present until its active metabolite, norfluoxetine, has been cleared. This can take 6 weeks or more depending on the daily dose of fluoxetine that has been used, as well as the age and health of the patient. 

To illustrate this problem, studies done with fluoxetine are reviewed here in greater detail. This SSRI is perhaps the best studied with regard to the issue of teratogenicity. The reason is related both to its widespread use in women of childbearing potential and to the extended half-life of its active metabolite, norfluoxetine. Even though most physicians will stop medications whenever feasible in a woman who becomes pregnant, the long half-life of norfluoxetine means that it will persist in... 

Available evidence suggests that due to this better tolerability, SSRIs are the best choice for patients with PD ( 113). SSRIs also offer benefits of ease of dosing and no safety or dependence problems. This contrasts with the poor tolerance associated with TCAs and with dependence problems associated with BZDs ( 114). In addition, because of the longer half-life, fluoxetine at doses ranging from 10 to 60 mg administered once weekly appears to be an effective maintenance treatment for patients with PD whose successful initial treatment was with daily fluoxetine (115). 

The drug has a half-life of 6-8 hours. It is extensively metabolized in the liver, and stereoselective metabolism of its two isomers is observed. Since metabolism of ( R)-carvedilol is influenced by polymorphisms in CYP2D6 activity and by drugs that inhibit this enzyme s activity (such as quinidine and fluoxetine, see Chapter 4), drug interactions may occur. Carvedilol also appears to attenuate oxygen free radical-initiated lipid peroxidation and to inhibit vascular smooth muscle mitogenesis independently of adrenoceptor blockade. These effects may contribute to the clinical benefits of the drug in chronic heart failure (see Chapter 13). 

The prototype SSRI, fluoxetine, differs from other SSRIs in some important respects (Table 30-1). Fluoxetine is metabolized to an active product, norfluoxetine, which may have plasma concentrations greater than those of fluoxetine. The elimination half-life of norfluoxetine is about three times longer than fluoxetine and contributes to the longest half-life of all the SSRIs. As a result, fluoxetine has to be discontinued 4 weeks or longer before an MAOI can be administered to mitigate the risk of serotonin syndrome. 

Fluoxetine (Prozac] Moderate, selective inhibition of serotonin reuptake No sedative, anticholinergic, or cardiovascular side effects helpful in obsessive-compulsive disorder May cause anxiety, nausea, insomnia long half-life can lead to accumulation... 

The pharmacokinetic parameters of these drugs are summarized in Table 30-2. Fluoxetine is notable for the long half-life of its active metabolite, norfluoxetine (7-9 days at steady state). This long 11/2 has allowed for the introduction of a formulation for once-weekly dosing. Fluoxetine... 

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