Pharmacokinetics of Fluoxetine in Elderly Men and Women

Ferguson, James M.; Hill, Heather

doi:10.1159/000089825

Cited by 32 publications

(25 citation statements)

References 17 publications

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“…There is little published information on sex differences in the metabolism of fluoxetine in humans. In one study, elderly males and females did not differ in plasma concentrations of fluoxetine, but women had significantly higher levels of norfluoxetine than men and slower clearance of norfluoxetine (Ferguson and Hill, 2006). This pattern is similar to the one measured here in mice and suggests that activational reproductive hormones are not necessary for sex differences in fluoxetine metabolism.…”

Section: Sex Differences In Neurogenesis Induced By Fluoxetine 271supporting

confidence: 52%

Sex-Specific Effects of Chronic Fluoxetine Treatment on Neuroplasticity and Pharmacokinetics in Mice

Hodes

Hill-Smith²,

Suckow³

et al. 2009

J Pharmacol Exp Ther

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Neurogenesis is a mechanism through which antidepressants may produce therapeutic effects. There is a dearth of information regarding the effects of antidepressants on neurogenesis and neurotrophin mobilization in females. This study examined sex differences in the alteration of cell proliferation and survival in multiple regions of the brain. Additional experiments examined brain-derived neurotrophic factor (BDNF) levels and pharmacokinetics of fluoxetine to determine whether they mediate sex differences. MRL/MpJ mice were treated with fluoxetine (5 and 10 mg/kg b.i.d.) for 21 days and received injections of 5-bromo-2Ј-deoxyuridine (200 mg/kg) to measure DNA synthesis. In the hippocampus, fluoxetine increased cell proliferation at both doses; females treated with 10 mg/kg produced more new cells than males. Fluoxetine did not alter survival in males, but 10 mg/kg reduced survival in females. In the frontal cortex, fluoxetine increased cell proliferation and survival in males treated with 10 mg/kg. In the cerebellum and amygdala, 10 mg/kg fluoxetine increased cell proliferation in both sexes but did not alter the incorporation of the new cells. Fluoxetine increased BDNF levels in the hippocampus of both sexes. BDNF levels correlated with cell proliferation in males but not females. Brain and plasma levels indicated that females metabolized fluoxetine faster than males and produced more of the metabolite norfluoxetine. These data suggest that fluoxetine acts on multiple areas of the brain to increase cell proliferation, and the pattern of activation differs between males and females. Sex-specific effects of fluoxetine on neurotrophin mobilization and pharmacokinetics may contribute to these differences in neural plasticity.

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Section: Sex Differences In Neurogenesis Induced By Fluoxetine 271supporting

confidence: 52%

Sex-Specific Effects of Chronic Fluoxetine Treatment on Neuroplasticity and Pharmacokinetics in Mice

Hodes

Hill-Smith²,

Suckow³

et al. 2009

J Pharmacol Exp Ther

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“…Mice of three different groups of age received fluoxetine daily in a dosage leading to clinically relevant plasma concentrations over a long period of time to mimic chronic treatments administered to human patients. 32,33 In young animals, we could confirm that fluoxetine promotes neurogenesis, as a result of an enhancement of survival of newly generated cells and a cell fate shift towards neuronal phenotypes. Fluoxetine, however, neither enhanced the proliferation rate of progenitors in the hippocampus of young animals nor in old animals.…”

Section: Discussionmentioning

confidence: 68%

“…In mice, this dosage has been reported to yield fluoxetine serum levels, which are comparable to those observed in patients receiving fluoxetine as antidepressant medication. 32,33 Control animals received volume-matched injections of PBS. For the analysis of cell proliferation, mice received a single injection of BrdU at 200 mg kg À1 of body weight on day 28 and 2 h later mice were perfused under deep anesthesia with a pH 7.4 phosphate-buffered 4% paraformaldehyde solution.…”

Section: Animalsmentioning

confidence: 99%

Ageing abolishes the effects of fluoxetine on neurogenesis

et al. 2009

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Depression constitutes a widespread condition observed in elderly patients. Recently, it was found that several drugs employed in therapies against depression stimulate hippocampal neurogenesis in young rodents and nonhuman primates. As the rate of neurogenesis is dramatically reduced during ageing, we examined the influences of ageing on neurogenic actions of antidepressants. We tested the impact of fluoxetine, a broadly used antidepressant, on hippocampal neurogenesis in mice of three different age groups (100, 200 and over 400 days of age). Proliferation and survival rate of newly generated cells, as well as the percentage of cells that acquired a neuronal phenotype were analyzed in the hippocampus of mice that received fluoxetine daily in a chronic manner. Surprisingly, the action of fluoxetine on neurogenesis was decreasing as a function of age and was only significant in young animals. Hence, fluoxetine increased survival and the frequency of neuronal marker expression in newly generated cells of the hippocampus in the young adult group (that is 100 days of age) only. No significant effects on neurogenesis could be detected in fluoxetine-treated adult and elderly mice (200 and over 400 days of age). The data indicate that the action of fluoxetine on neurogenesis is highly dependent on the age of the treated individual. Although the function of neurogenesis in the clinical manifestation of depression is currently a matter of speculation, this study clearly shows that the therapeutic effects of antidepressants in elderly patients are not mediated by neurogenesis modulation.

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“…However, despite extensive scientific literature describing its efficacy and safety, there is little published data describing the pharmacokinetics of this drug in the elderly. However, Ferguson and Hill (2006) performed a study of the plasma concentration of fluoxetine and norfluoxetine in such subjects, and observed a higher concentration than previously reported in the literature, due to the longer elimination half-life in the elderly. Thus, these high levels of fluoxetine in the plasma of elderly patients may lead to toxic effects (Ferguson, Hill, 2006), producing excessive central nervous system stimulation, sleep disturbances and increasing agitation (Fick et al, 2003).…”

Section: · Selective Serotonin Reuptake Inhibitors (Ssris)mentioning

confidence: 79%

Elderly and drugs: risks and necessity of rational use

Baldoni

Chequer

Ferraz

et al. 2010

Braz. J. Pharm. Sci.

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In recent decades, the world has undergone a demographic transformation with a rapid growth of the elderly population, resulting in an increased demand for funds to maintain their health and drug consumption. Pharmacokinetic and pharmacodynamic changes occurring in the elderly can interfere directly in the adverse effects of drugs and increase the risk of intoxication. In addition, there are external factors interfering with the pharmacotherapy of the elderly, such as inappropriate use and the lack of access to information. Many therapeutic classes of drugs should be used with caution or avoided in the elderly population, such as anti-inflammatory and some anti-hypertensive drugs, diuretics and digitalis. If not managed carefully, these medicines can affect the safety and quality of life in the elderly. Thus, the aim of this review was to identify drugs that should be used with caution in elderly patients in order to avoid intoxication and/or adverse drug events.Uniterms: Elderly/inappropriate medicines. Medicines/consumption. Medicines/adverse reaction. Medicines/intoxication. Medicine/rational use. Medicine/inappropriate prescribing.Durante as últimas décadas, o mundo passou por uma transformação demográfica, com um rápido crescimento da população idosa e, portanto, tanto a demanda para a manutenção da saúde deste grupo populacional, quanto o consumo de medicamentos estão aumentando. Ainda, as mudanças farmacocinéticas e farmacodinâmicas que ocorrem em idosos podem interferir diretamente nos efeitos adversos dos medicamentos e aumentar o risco de intoxicação. Além disso, há fatores externos que interferem na farmacoterapia dos idosos, tais como o uso inadequado e a falta de acesso à informação. Existem várias classes terapêuticas de medicamentos que devem ser utilizados com cautela ou evitados na população idosa, tais como antiinflamatórios, alguns anti-hipertensivos, diuréticos, digitálicos entre outros. Estes medicamentos, se não forem utilizados com cuidado, podem afetar a qualidade de vida e a segurança desta população. Assim, este trabalho visa identificar medicamentos que devem ser utilizados com cuidado em pacientes idosos para evitar intoxicações e/ou eventos adversos aos medicamentos.Unitermos: Idosos/medicamentos inadequados. Medicamentos/consumo. Medicamentos/reação adversa. Intoxicação medicamentosa. Medicamentos/uso racional. Prescrição inapropriada.

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Pharmacokinetics of Fluoxetine in Elderly Men and Women

Cited by 32 publications

References 17 publications

Sex-Specific Effects of Chronic Fluoxetine Treatment on Neuroplasticity and Pharmacokinetics in Mice

Sex-Specific Effects of Chronic Fluoxetine Treatment on Neuroplasticity and Pharmacokinetics in Mice

Ageing abolishes the effects of fluoxetine on neurogenesis

Elderly and drugs: risks and necessity of rational use

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