Sertraline half-life

Elderly Clearance of fluvoxamine is decreased by about 50% in elderly patients. A lower starting dose of paroxetine is recommended. Sertraline plasma clearance may be lower. In 2 pharmacokinetic studies, citalopram AUC was increased by 23% and 30%, respectively, in elderly subjects as compared with younger subjects, and its half-life was increased by 30% and 50%, respectively. In 2 pharmacokinetic studies, escitalopram half-life was increased by approximately 50% in elderly subjects as compared with young subjects and C ax was unchanged. 

Sertraline pharmacokinetics were described in 61 children and adolescents (ages 6 to 17) with depression or OCD (Alderman et ah, 1998). Mean area under the plasma concentration-time curve, peak plasma concentration, and elimination half-life for sertraline and des-methylsertraline were similar to previously reported adult values. No differences between children and adolescents were apparent when values were normalized for body weight. 

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. 

Sertraline hydrochloride has an average half-life of about 26 hours, and mean peak plasma concentrations occur at 4.5-8.4 hours. The dosage is 50-200 mg/day orally. Its major metabolite, /V-desmethylsertraline, is less active than sertraline. Adverse effects are as for the SSRIs in general. 

Another difference between the SSRI antidepressants is their half-lives. Paroxetine has a half-life of approximately one day, sertraline one to two days, and fluoxetine seven to ten days. A long half-life is an advantage in maintaining a stable blood level but a disadvantage when starting or stopping the mediciaton. It takes six weeks to reach a steady state with fluoxetine. 

Sertraline s bioavailability is reduced by extensive first-pass metabolism. The principal metabolite of this first-pass metabolism is N-desmethylsertraline. N-Desmethylsertraline has a half-life of 62-104 h and is substantially less active than the parent compound. Sertraline and its metabolite N-desmethylsertraline both undergo further biotransformation to nonactive compounds. Clearance of sertraline may be faster in children than in young adults and slowest in the elderly. 

Sertraline and fluoxetine undergo metabolic demethylation. Unlike the metabolites of most other SSRIs, the desmethyl metabolite of fluoxetine, norfluoxetine(34), retains the ability to inhibit serotonin reuptake (205). Hence, fluoxetine takes longer to achieve steady-state levels, and it retains activity after metabolism. The half-life of fluoxetine is approximately 1 day, but elimination of norfluoxetine is prolonged (7-15 days) (205). In addition to its actions as an SSRI, norfluoxetine also binds at 5-HT, receptors (127). 

The diversity of the SSRIs is evident not only in their chemical structures, but also in their pharmacokinetic profiles. Fluoxetine has an elimination half-fife of 2 to 3 days (4 to 5 days with multiple dosing). The single-dose hah-hfe of norfluoxetine, the active metabolite, is 7 to 9 days. Paroxetine and sertrahne have half-lives of approximately 24 hours. Unlike paroxetine, sertraline has an active metabolite, but the metabohte contributes minimally to the pharmacologic effects. Escitalopram has a half-life of approximately 30 hours. Peak plasma concentrations of citalopram are observed within 2 to 4 hours after dosing, and the elimination half-life is about 30 hours. The SSRIs, with the exception of fluvoxamine, escitalopram, and citalopram, are extensively bound to plasma proteins (94% to 99%). The SSRIs are extensively distributed to the tissues, and aU, with the possible exception of citalopram, may have a nonlinear pattern of drug accumulation with long-term administration. ... 

In cirrhotics, the half-lives of fluoxetine and norfluoxetine increased to 7.6 and 12 days, respectively. Patients with hepatic impairment had a twofold increase in plasma concentrations of paroxetine. Similarly, in patients with mild stable cirrhosis, the half-life of sertraline was 2.5 times greater than in patients without liver disease. Patients with renal impairment had a two- to fourfold increase in paroxetine plasma concentrations compared with normal volunteers. Plasma concentrations of SSRIs in the elderly are reported to be greater than in younger patients. ... 

Selective serotonin reuptake inhibitors (SSRIs) Fluoxetine is the prototype of a group of drugs that selectively inhibit the reuptake of serotonin. AH of them require hepatic metabolism and have half-lives of 18—24 hours. However, fluoxetine forms an active metabolite with a half-life of several days. Other members of this group (eg, sertraline, citalopram, paroxetine), do not form long-acting metabolites. 

In a randomised, two-way, crossover study, 12 healthy subjects were given a single 100-mg oral dose of sertraline after taking either cimetidine 800 mg or a placebo at bedtime for 7 days. Cimetidine increased the AUC of sertraline by 50%, the maximum serum levels of sertraline by 24%, and the half-life by 26%. There was a small increase in sertraline adverse effects (not specified) while taking the cimetidine. ... 

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