GASTROINTESTINAL ABSORPTION IN MAN AS A FUNCTION OF AGE: DISPOSITION OF D-XYLOSE AS A MODEL COMPOUND (BIOAVAILABILITY).

Abstract

The purpose of this study was to examine the pharmacokinetics of d-xylose in man as a function of age with particular emphasis on its absorption characteristics. This study required the development of a specific and sensitive method for the quantitation of xylose from plasma and urine. Following a clean-up procedure, plasma or urine samples are concentrated and undergo two sequential derivatization steps and then are quantitated by capillary column gas liquid chromatography (GLC). D-Xylose is frequently quantitated by a tedious colorimetric assay involving the use of thiourea, a proven animal carcinogen. We have evaluated a more expedient colorimetric assay employing less toxic reagents. Based upon these comparisons the "phloroglucinol" method has been recommended as a replacement for the currently used clinical method for quantitating d-xylose. The human studies revealed age related changes in some but not all d-xylose disposition parameters. Systemic, renal, and nonrenal clearances all declined with advancing age. The terminal elimination half life increased with age. Age had very little influence on the various volumes of distribution. In general, parameters relating to oral absorption showed no age-related dependence. In contrast to what is generally believed, the bioavailability of d-xylose did not decline with age. Lastly, this dissertation addresses the problem of how infusion data may best be fit. Concentration-time data may be fit by a nonlinear regression algorithm in two ways; (1) concentration-time data may be collected and fit both during infusion and after infusion is terminated, (2) concentration-time data may be collected only after the infusion is terminated and be fit as a bolus. Concentration-time data were computer simulated with random error and we found that fitting the entire curve gave the most accurate estimates of disposition parameters.