Xylitol—Clinical Pharmacology in Normal Adult Volunteers

¹ Department of Clinical Research and the Department of Clinical Pharmacology, Abbott Laboratories, North Chicago, Ill. 60064.

The data show a positive dose response between xylitol and serum uric acid. A single 2-hour infusion of 25 Gm xylitol (500 cc of 5% xylitol) caused an elevation of serum uric acid which did not go above the normal range, but which was certainly an absolute elevation (refer to the sampling points shown for the first infusion in Fig. 3). A single 2-hour infusion of 100 Gm xylitol (1000 cc of 10% xylitol) caused an even greater elevation of serum uric acid, but which again did not go out of the normal range (refer to the sampling points for the first infusion shown in Fig. 2).

Two infusions of xylitol per day caused an elevation of serum uric acid above the normal range by the second or third day (two infusions of 25 Gm each—see Fig. 3) or even by the first or second day (two infusions of 100 Gm each—see Fig. 2), depending on the individual.

The 24-hour urinary excretion of uric acid was doubled when the volunteers received two 100-Gm infusions of xylitol per day.

Simultaneous infusions of dextrose did not alter the elevation of serum uric acid as caused by xylitol.

The data show an elevation of total bilirubin and an interference with bilirubin conjugation that we speculate is dose related, but we can only show it for single and multiple infusions of 100 Gm xylitol each (Figs. 4 and 5). More importantly, we feel that the range of responses shown in Fig. 4 may be an indication of the general population's broad spectrum of sensitivity to xylitol.

We feel that the variation in the degree of upper gastrointestinal symptoms leading to nausea and vomiting in our volunteers is also an example of a spectrum of response and that volunteer C.B.G. represents a person with unusual sensitivity.

We have insufficient data to speculate about the possible mechanisms responsible for the uric acid, bilirubin, and clinical symptoms, or to suggest positive or negative relationships between the three findings.

We cannot explain why similar findings have not been reported previously with xylitol. It is our feeling, however, that two factors may have contributed. One is that the correct timing and particularly sufficient frequency of blood sampling may not have been undertaken to alert someone to the changes. (Reference to Fig. 4 will show that samples taken only at 24-hour intervals would have missed the changes completely.) The other is that different dosing schedules coupled with differences in individual sensitivity could cause the occasional etiologic relationship of xylitol to mild liver problems or gastrointestinal symptomatology to be overlooked in a patient whose basic illness might also lead to these same changes.

Edwards et al. have described problems arising in patients after xylitol was in widespread use in Australia.^19-21 The study of intravenous xylitol in this country has been discontinued as a result of our studies.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?