Drug Biotransformation Interactions in Man II: A Pharmacokinetic Study of the Simultaneous Conjugation of Benzoic and Salicylic Acids with Glycine

Conjugation and urinary excretion of toluene and m-xylene metabolites in a man

“…If, however, the full conjugating capacity is occupied, the excretion of toluene and xylene metabolites will inevitably be delayed. Because the tubular secretion capacity for hippurates is at least two times larger than the capacity for hippurate formation (1,20), renal excretion, under conditions of normal kidney physiology, will not determine the excretion kinetics of toluene or xylene, contrary to what has been proposed (19).…”

“…Because benzoates seem to be good substrates for glycine conjugation, the consequence may well be a disturbance in the metabolism of the competing compound. For instance, it was shown that saturation of glycine conjugation with benzoate hinders normal biotransformation and hence excretion of salicylic acid so that the drug may hazardously cumulate in the body (1,8). Furthermore, it has been known for a long time that ingesting greater amounts of benzoic acid decreases the renal excretion of uric acid 1 (14).…”

“…Benzoic acid is, in man, almost completely conjugated with glycine and excreted as hippuric acid via the kidneys (14). The conjugation reaction may become ratelimited by the availability of glycine (1,14). The mobilization of endogenous glycine was estimated nearly 50 years ago to take place maximally at a rate of 122-155 /Imol!min, depending on body size (14), but more recent data indicate that the maximum rate of hippurate formation is about 190 jlrnol/min (1) and that it can be considerably increased by an additional supply of exogenous glycine.…”

“…The conjugation reaction may become ratelimited by the availability of glycine (1,14). The mobilization of endogenous glycine was estimated nearly 50 years ago to take place maximally at a rate of 122-155 /Imol!min, depending on body size (14), but more recent data indicate that the maximum rate of hippurate formation is about 190 jlrnol/min (1) and that it can be considerably increased by an additional supply of exogenous glycine. In some spe-cies benzoic acid is primarily conjugated with glucuronic acid (3), and even in man increasing doses of benzoic acid, from 6.9 to 69 mmol, increase the proportion of glucuronidation from 0.4 to 3.0°/0 of the total conjugation (16).…”

Scientific Opinion on Flavouring Group Evaluation 20, Revision 2 (FGE.20Rev2): Benzyl alcohols, benzaldehydes, a related acetal, benzoic acids, and related esters from chemical groups 23 and 30

“…Minor amounts of benzoyl glucuronide were detected at both doses. Co-administration of glycine with benzoate increased the rate of hippuric acid excretion, indicating that at high dose levels, glycine is rate limiting for formation of hippuric acid (Amsel & Levy, 1969).…”