Pharmacokinetics in the elderly

1We examined the case notes of 82 psychiatric out-patients (aged 21-84 years) receiving lithium prophylaxis and with steady-state plasma lithium levels. 2 The mean weight-related daily dose of lithium prescribed decreased by about 50% between the third and eighth decades. 3 The corresponding steady-state plasma lithium levels showed a less marked tendency to decrease, this only being seen in the seventh and eighth decades. 4 In patients aged 50 years or over the daily lithium dose required to give a plasma level of 1 mmol 1-1 (0.50 mmol kg-') was significantly lower than that (0.65 mmol kg-') in patients aged under 50 years (P < 0.005, Student's t-test). In patients aged 70-79 years this dose was 31 % lower than in patients under 50 years. However, interindividual variation was great and it was estimated that age only contributed about 14% to the total interpatient variation. 5Of the 36 patients under 50 years of age, 42% had minor lithium side-effects and 17% were not optimally controlled with lithium. The corresponding figures for the 46 'older' patients were 46% and 28%. 6 Generally the 50% dosage reduction seemed necessary to compensate for an age-related decrease in lithium excretion and to reduce lithium side effects to a level comparable to that acceptable in younger patients.

Section: Discussionmentioning

confidence: 99%

Age as a factor affecting lithium therapy.

Hewick¹,

Newbury²,

Hopwood³

et al. 1977

“…Re-shown that some NSAIDs (e.g. benoxaprofen, duced metabolism of some drugs also occurs phenylbutazone) have altered disposition in the elderly (Hamdy et al, 1982;Triggs et al, 1975). Other drugs however such as indomethacin and fenbufen show little change in their pharmacokinetics (Crooks et al, 1983;Braverman, 1982).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic profile of controlled release ketoprofen in elderly patients.

Dennis¹,

Pc²,

Crome³

et al. 1985

The pharmacokinetics of ketoprofen following the administration of the first and final dose of a controlled release formulation (200 mg ketoprofen) once daily for 10 days to nine elderly patients have been studied. Plasma ketoprofen concentrations were measured by h.p.l.c. The data were compared to previously reported studies in young male volunteers. Mean +/‐ s.d. peak plasma concentrations (5.6 +/‐ 1.75 micrograms ml‐1 and 6.3 +/‐ 2.7 micrograms ml‐1 on day 1 and day 10, respectively) were higher than those reported in young volunteers given similar treatment, but similar to those reported in young volunteers following 50 mg four times daily of conventionally formulated ketoprofen, and markedly lower than reported following a single 100 mg dose of ketoprofen. The half‐life for drug release (mean +/‐ s.d.) from the controlled release formulation (8.5 +/‐ 7.4 h) and accumulation upon repeated dosing (28%) were essentially the same as reported for young volunteers. The area under the plasma concentration‐time curve was about 65% greater than reported in young volunteers following administration of controlled release ketoprofen. This increase in exposure to ketoprofen is probably partly due to the lower volume of distribution in the elderly and partly due to a reduced renal excretion of the glucuronide metabolite of ketoprofen. It was concluded that controlled release ketoprofen may be administered in standard doses (200 mg once daily) to elderly patients whose elimination processes are not severely impaired (i.e. severe renal failure or hepatic disease).(ABSTRACT TRUNCATED AT 250 WORDS)

“…Of more importance is the impairment of renal function in old age, causing increased plasma concentrations of drugs which are excreted by the kidney (Crooks et al, 1976). A change in apparent volume of distribution (Nation, Learoyd, Barber & Triggs, 1976) and diminished activity of metabolising enzymes in the liver may also be involved (Triggs, Nation, Long & Ashley, 1975;Reynolds, Wilson & Burnett, 1978). Obviously, more than one of these factors may be responsible for the changes in pharmacokinetics noted in the elderly.…”

Section: Introductionmentioning

confidence: 99%

The effect of age on the pharmacokinetics of metoprolol and its metabolites.

Quarterman¹,

Kendall²,

DeRuiter³

1981

1Plasma concentrations of metoprolol and a pharmacologically active metabolite, H119/66, have been measured in young and elderly volunteers after a single dose of 100 mg metoprolol tartrate and after repeated administration over a period of 1 week. Whilst concentrations of metoprolol are similar in each group, concentrations of H119/66 are approximately twice as high in the elderly. 2 Concentrations of unchanged metoprolol and of the major, but pharmacologically inactive, metabolite, H117/04, together with the two active metabolites of metoprolol have been determined in urine. Only the excretion of metoprolol was diminished in the elderly. 3 Areas under the plasma concentration curve for metoprolol after repeated administration are greater than would be predicted from single dose data, and possible explanations for this are discussed. Concentrations of the pharmacologically active metabolite, H119/66, remain unaltered during chronic dosing of metoprolol. 4 This study has shown that the effect of age on the pharmacokinetics of metoprolol and its metabolites is less pronounced than that observed for other drugs.