Observations on Lithium Disposition in the Elderly

Chapron, Dennis J.; Cameron, I. R.; White, Lorraine B.; Merrall, Pauline

doi:10.1111/j.1532-5415.1982.tb05064.x

Cited by 17 publications

(9 citation statements)

References 13 publications

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“…Mason et al (1978) estimated the elimination half-life in a group of schizophrenic patients to be, on average, 28.9 h, and as in our study there were considerable interindividual variations. Chapron et al (1982) found similar values in a group of elderly women with affective disorders in whom the mean treatment time with lithium was 3 years. Nielsen-Kudsk and Amdisen (1979) demonstrated an elimination half-life of 19.8 h in healthy volunteers, but the interindividual difference was substantial.…”

Section: Discussionsupporting

confidence: 82%

On the elimination half‐life of lithium in long‐term treatment of patients with affective disorders

Nilsson¹,

Axelsson²

1989

Human Psychopharmacology

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The elimination half‐life of lithium was investigated in 55 patients on long‐term treatment in 1980, when their mean treatment time was 7·5 years. Twenty‐seven of the patients were reinvestigated 7 years later, at which point their mean treatment time was 15 years. An approximate method for determining the elimination half‐life of lithium was used, and this variable was tested in eight chronic psychotic patients on lithium treatment, in whom the elimination half‐life was also determined by a conventional technique. The elimination half‐life was 32 h in 1980 and varied between 15 and 128 h. The elimination half‐life was significantly increased 7 years later, with a median increase of 8 h. The elimination half‐life of lithium was closely correlated to age and to daily weight‐related dose of lithium when the patients entered the study in 1980, but this was not seen at the time of the reinvestigation in 1987. The elimination half‐life did not vary with serum creatinine, maximal urine osmolality, or with the concomitant neuroleptic medication. Further studies are needed to clarify the clinical significance of the prolonged elimination half‐life with time.

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Section: Discussionsupporting

confidence: 82%

On the elimination half‐life of lithium in long‐term treatment of patients with affective disorders

Nilsson¹,

Axelsson²

1989

Human Psychopharmacology

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“…Inclusion of children in their study or the confounding influence of concurrent heart disease could account for the discrepancy. Previous studies from our laboratory have shown that the ratio of renal drug clearance to creatinine clearance is similar between young and old adults for theophylline (Antal et al, 1981) and lithium (Chapron et al, 1982). The rate of excretion of an intravenous dose of AZ was nearly identical for old and young (Figure 3).…”

Section: Discussionmentioning

confidence: 65%

Influence of advanced age on the disposition of acetazolamide.

Chapron¹,

Sweeney²,

Feig³

et al. 1985

Brit J Clinical Pharma

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1 The disposition kinetics of acetazolamide (AZ) has been studied in four young and four elderly healthy volunteers, each of whom received an intravenous bolus dose of 5 mg/kg. The concentration time profile of AZ was determined in plasma, plasma ultrafiltrate, erythrocytes and urine. 2 While the mean area under unbound plasma concentration-time curves was 81% higher in elderly subjects, areas based on total drug concentrations were similar in both groups. The mean renal plasma clearance was similar in both groups. The mean renal plasma clearance was similar between young and old for total AZ, but was significantly lower in the elderly for unbound drug (8.88 ml min-' kg-' vs 15.7 ml min-' kg-'). Renal clearance of unbound AZ correlated well with creatinine clearance (r = 0.846, P < 0.01). 3 Peak erythrocyte levels were 45% higher in the elderly group (37.2 ,g/ml vs 25.3 jig/ml) and were paralleled by a 46% increase in the mean area under the erythrocyte concentration-time curve for this age group. The unbound fraction of AZ in plasma was significantly greater in elderly than younger subjects (6.9 vs 4.1%, P < 0.05). Integrated AZ erythrocyte concentrations correlated positively with AZ free fraction in plasma and inversely with its unbound renal clearance. These observed differences in AZ disposition between elderly and young have served to clarify host factors which may importantly influence susceptibility to adverse effects.

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“…Case notes from 82 patients (21 to 84 years) were reviewed for lithium concentrations, demographic information, concurrent medications or medical conditions and clinical assessments. Chapron et al (1982) reported on 6 female patients aged 73 to 88 years who had been treated with varying doses of lithium for 2 to 5 years. A less marked decline in CSs occurred with increasing age.…”

Section: Lithiummentioning

confidence: 99%

Clinical Pharmacokinetics of Antidepressants in the Elderly

Moltke

Greenblatt

Shader

1993

Clinical Pharmacokinetics

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The prevalence of depression in the elderly suggests that a substantial number of older patients will be treated with an antidepressant medication such as one of the tricyclics, trazodone, fluoxetine or lithium. The physiological changes that accompany aging raise the possibilities of altered pharmacokinetics, patterns of efficacy and adverse effect profiles. The literature addressing the subject of antidepressant use in the elderly has not provided a clear, consistent picture of how these drugs behave in this population in comparison with younger patients. Particularly in the case of the tricyclic antidepressants (TCAs), a large degree of interindividual variation in drug clearance (CL) confounds attempts to find differences attributable to age per se. Study design, however, is also a problem in that very few investigators include a young control group, choosing instead to compare their data with previously reported outcomes. Designations of statistical significance and positive correlation also differ among investigators, and the clinical significance of any finding is not always addressed. The available data suggest that imipramine CL is reduced in the elderly and that amitriptyline CL may be reduced. Desipramine CL does not appear to be affected by age, although decreased renal function in the elderly may lead to accumulation of the hydroxylated metabolite, the clinical importance of which is not known. Nortriptyline is the most thoroughly studied TCA in the elderly. CL seems decisively lower only in elderly patients with concurrent medical illness. The hydroxylated metabolite probably accumulates with diminishing renal function. Not enough data are available on doxepin to make a conclusion. Trazodone CL is diminished somewhat in elderly men. Lithium CL appears to diminish with the declining renal function associated with aging. Fluoxetine data are sparse. Available data do not show any decrease in CL of the parent drug; more information is needed on the metabolite norfluoxetine. Although knowledge of CL changes with aging can help the clinician more accurately achieve the desired steady-state concentration of a drug during long term therapy, much work is still needed to evaluate the relationships among drug concentrations at steady-state, efficacy and adverse effects in the elderly.

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Observations on Lithium Disposition in the Elderly

Cited by 17 publications

References 13 publications

On the elimination half‐life of lithium in long‐term treatment of patients with affective disorders

On the elimination half‐life of lithium in long‐term treatment of patients with affective disorders

Influence of advanced age on the disposition of acetazolamide.

Clinical Pharmacokinetics of Antidepressants in the Elderly

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