Theophylline kinetics in a geriatric group

Abstract

The influence of age, sex, and smoking on theophylline disposition was studied in 38 healthy subjects ranging in age from 26 to 81 yr. There were 8 young (less than 60 yr) and 30 geriatric (greater than 60 yr) subjects, including 28 men (8 smokers) and 10 women (3 smokers). A crossover experimental design was used. A single dose of theophylline elixir (5 mg/kg lean body weight [LBW]) was given as a reference product to all subjects. One week later a sustained-release (SR) theophylline tablet (8 and 6 mg/kg LBW) was given to the young and the geriatric subjects. Serum theophylline concentrations were determined by HPLC. Theophylline elimination (t1/2 beta) is shorter in the geriatric group (6.93 and 8.14 hr); total body theophylline clearance is greater in the geriatric group (44.39 and 32.97 ml/kg/hr), and the apparent volume of distribution is also greater in the geriatric group (26.29 and 22.97 l). Sex and smoking did not influence any of the parameters studied. In 93% of the geriatric subjects, serum theophylline levels of 8 to 20 micrograms/ml were reached at steady state with the SR tablet. Theophylline dose reduction based on an arbitrary age limit is not, therefore, invariably indicated.

Pharmacokinetics of an ultralong sustained‐release theophylline formulation when given twice daily in elderly patients with chronic obstructive pulmonary disease: Monitoring implications

“…However, the results of our study were unable to demonstrate a significant correlation between apparent clearance and age in elderly patients either when all patients or when only patients without any factor affecting theophylline clearance were taken into account. The lack of influence of age seen in our study in patients 60-87 years old does not agree with the results of other investigators who reported a reduction in theophylline clearance [28] or an increase in the concentration-to-dose ratio with age [21] but it does agree with the results of other studies that did not find a significant reduction in theophylline clearance with age in patients of a similar age to those of our study [22,25].…”

“…Antal et al [22] did not find a significant reduction in theophylline clearance with age when the total plasma theophylline was monitored but it became apparent when unbound theophylline was taken into account. Although other investigators did not find significant differences in theophylline clearance between the elderly and the younger adult [23][24][25][26], a reduction in theophylline dosage with age has been proposed in a nomogram to individualize theophylline dosage in the elderly [27] and a reduction of theophylline dosage of 15-25% has been recommended in patients aged 75 years in relation to those aged 50 years [21]. However, the results of our study were unable to demonstrate a significant correlation between apparent clearance and age in elderly patients either when all patients or when only patients without any factor affecting theophylline clearance were taken into account.…”

Effects of time of dosing and age on intravenous aminophylline pharmacokinetics.

“…Previous work has failed to resolve the question of age related changes in kinetics. Several workers have suggested that clearance falls with ageing (Nielsen-Kudsk et al, 1978;Jusko et al, 1979;Talseth et al, 1981) although these findings have been considered by Fox, who found increased clearance in older subjects (Fox et al, 1983). There have been several claims for unchanged elimination (Cusack et al, 1980;Bauer & Blouin, 1981;Blouin et al, 1981) and Antal et al (1981) suggested that clearance was significantly diminished only if protein binding was taken into account.…”

“…Although the diurnal kinetics of aminophylline are well established in young subjects (Ogilvie, 1978), work in the elderly has produced conflicting and contradictory results (Nielsen-Kudsk et al, 1978;Fox et al, 1983;Cusack et al, 1980). Little or no information is available regarding nocturnal theophylline kinetics in old subjects.…”

The effect of age on theophylline clearance in normal subjects.

“…Age has been reported by some investigators as having no effect on theophylline pharmacokinetics in an adult population (Cusack et al, 1980;Fox et al, 1983;Bauer & Blouin;, Powell etal., 1978. Other studies have indicated reduced theophylline clearance (Au et al, 1985) and increased steady-state trough plasma levels (Talseth etal., 1981) in the elderly.…”