Absorption and disposition of ampicillin in the elderly.

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Ampicillin (500 mg) was administered intravenously (i. v.) and orally to a small panel of young and elderly subjects in a cross-over fashion. Plasma concentrations of ampicillin were measured by a fluorimetric technique for 8 h following dosage. A two compartment-open model was used to characterise the plasma concentration-time data for the intravenous study, and a one compartment-open model incorporating an absorption lag time and a first-order absorption rate constant for the oral data. Plasma clearance after i. v. ampicillin was found to be significantly decreased in the elderly (P < 0.05, 0.08 1 h-1kg-1 versus 0.18 1 h-1 kg-1), and half life and area under the plasma level-time curve were significantly increased (P < 0.05, 6.70 h versus 1.68 h, t1/2 beta; p < 0.01, 176.51 microgram.h ml-1 versus 37.88 microgram.h ml-1, AUCO infinity) as compared to the young. No significant differences were observed between the age groups for the volume of distribution terms and the changes in drug handling noted in the elderly were attributed to a decrease in the renal elimination of ampicillin. Following oral administration a significant increase in t1/2 beta, AUCO infinity and the maximum plasma concentration (Cpmax P < 0.01, 6.59 microgram ml-1 versus 3.42 microgram ml-1) of amplicillin was found in the elderly subjects. These findings were similarly attributed to a decrease in drug elimination in the aged, since no apparent age differences were noted in the pharmacokinetic parameters governing both rate and extent of ampicillin absorption.