Age-related changes in drug absorption and metabolism

Robertson, Dorothy Ruth Caddick (1993) Age-related changes in drug absorption and metabolism. University of Southampton, Doctoral Thesis.

Abstract

Age-related changes in anatomy and physiology influence the way drugs are handled by the body. The aim of this thesis was to investigate the effect of age on drug absorption and metabolism using levodopa and nifedipine as model drugs.

The effect of age on the disposition of levodopa (given alone and with the peripheral dopa decarboxylase inhibitor carbidopa) was investigated in young and elderly `healthy' volunteers. The results in the elderly were compared with data obtained in middle aged volunteers to determine whether the pharmacokinetics of levodopa alter over the age range normally affected by Parkinson's disease. The first pass metabolism and systemic clearance of levodopa were lower in the elderly compared with the young volunteers.

The age difference in bioavailability was abolished by carbidopa, consistent with an age-related decline in decarboxylase activity. Carbidopa reduced the plasma clearance of levodopa in both age groups but the age difference in clearance remained. No significant differences in levodopa plus carbidopa pharmacokinetics were observed between the middle aged and elderly subjects. This suggests that pharmacodynamic factors rather than age-related pharmacokinetic changes are responsible for the therapeutic problems seen with elderly parkinsonian patients.

Plasma clearance values for both drugs indicate `flow-dependent' pharmacokinetics. Age-related changes in blood flow probably account for the observed decline in their plasma clearance. The fall in liver size with age and/or reduced enzyme activity may explain the reduction in first pass metabolism of these drugs in the elderly. The relative importance of these factors remains uncertain.

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