Clinical pharmacology and the elderly patient

O’Malley, K; Laher, M; Cusack, Barry J.; Kelly, J.G.

doi:10.1007/978-94-011-6223-4_1

Cited by 7 publications

(8 citation statements)

References 107 publications

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“…While some of our results do not differ substantially from those of Cusack et al (1980) who compared healthy young controls with elderly patients in a long-term care setting, our conclusions are substantially different, primarily because age effects appear to have been masked by differences in plasma protein binding. While they reported that ageing per se did not' affect the absorption, distribution or elimination kinetics of single dose oral theophylline in non-smokers, we found significant differences in several parameters when measurements were based on unbound plasma theophylline determinations.…”

Section: Discussioncontrasting

confidence: 96%

“…Our observation that plasma clearance of total theophylline is unchanged in the elderly agrees with previously published results (Cusack et al, 1980). Unbound (intrinsic) clearance was, however, reduced by 30% in old age in our study, a finding that is probably more reflective of the actual level of metabolic activity in the two age groups.…”

Section: Discussionsupporting

confidence: 93%

“…Since 1-MX is a major metabolite of caffeine in man, residual caffeine could well have been producing the reported levels of 1-MX. It should also be noted in this regard that the kinetic study of Cusack in the elderly (Cusack et al, 1980) only withheld caffeine for 12 h prior to dosing. We have found that a washout period of48 h or longer is a necessity if accurate results are to be obtained.…”

Section: Discussionmentioning

confidence: 99%

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Theophylline pharmacokinetics in advanced age.

Antal¹,

Kramer²,

Mercik³

et al. 1981

Brit J Clinical Pharma

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1 Theophylline kinetics following a single oral dose were characterized and compared in non‐institutionalized ambulatory elderly and young gender‐matched control subjects. Study design stressed stringent, yet realistic, control of several external factors known to influence theophylline metabolism. 2 Plasma levels of total drug were significantly higher in the elderly only at early sampling times (0.5 and 1 h) and at 36 h, while unbound theophylline levels were significantly higher (P less than 0.05) at all sampling times resulting in a 45% greater AUC for unbound drug. 3 While no significant differences in volume of distribution (Vd) or overall plasma clearance were observed when calculations were based on total plasma theophylline, a 37% reduction in Vd (P less than 0.005) and a 30% reduction in overall plasma clearance (P less than 0.02) in the elderly became apparent when plasma protein binding was taken into account. 4 When urinary excretion patterns were compared, the elderly were found to have excreted a significantly higher fraction of the recovered dose as 1‐methyluric acid (P less than 0.01) and a lower fraction as unchanged theophylline (P less than 0.02). A 47% reduction in the renal clearance of unbound theophylline (P less than 0.005) was also observed in the elderly. 5 Results were consistent with less viable metabolism and renal excretion pathways for theophylline elimination in the elderly and serve to reemphasize the importance of including an assessment of plasma protein binding in studies of drug disposition in the elderly.

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Section: Discussioncontrasting

confidence: 96%

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Theophylline pharmacokinetics in advanced age.

Antal¹,

Kramer²,

Mercik³

et al. 1981

Brit J Clinical Pharma

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“…Approximately 5% of patient admittance to hospital with rheumatic disease were attributable to antirheumatic drug side effects 4 . The recognition of an apparent increase in side effects of drug therapy in elderly patients 5 followed the prophecy of physiologists and pharmacologists who described age‐related alterations in the absorption, distribution, metabolism, tissue receptors, and excretion of antirheumatic drugs in elderly subjects 6 …”

mentioning

confidence: 99%

“…Clinical pharmacologists have identified for us the pharmacological aberrations which may occur in the elderly 5, 6 …”

mentioning

confidence: 99%