Xenobiotic–urea conjugates; chemical or biological?

Abstract

1. Although the major pathways involved in drug metabolism have been elucidated, there remain those routes that may be considered as minor, esoteric, or even artifactual.

2. Conjugation with urea, an abundant, non-toxic, small water soluble molecule, is such a disputed and debatable Phase II pathway.

3. The present article collates data gleaned from the literature concerning xenobiotic–urea conjugation, presents pertinent information resurrecting the controversy and poses questions as to the nature of the phenomenon.

• Conjugation
• Phase II
• urea
• ureido radical

Notes

¹William Cruickshank (?–1811; FRS 1802), surgeon and chemist to the Woolwich Arsenal, London. Not to be confused with William Cumberland Cruikshank (1745–1800; FRS 1797), surgeon and anatomist, who lived and practised in London at the same time. After their deaths they were merged by historians into one man, with the former’s discoveries being ascribed to the latter (Neild, 1996).

²Cruickshank states nitrous acid; If to an ounce of this extract (urine residuum), be added an ounce of the concentrated nitrous acid, diluted with an equal quantity of water, a violent effervescence accompanied with heat, and the disengagement of nitrous gas will take place (p. 441) (Cruickshank, 1798). If this was indeed nitrous acid (“volatile nitric acid”, “phlogisticated nitric acid”), and not nitric acid, it would have changed quickly on contact with water to nitric acid and nitric oxide, the later on exposure to air would oxidise into nitrogen dioxide, a brown gas. Nitrous acid may also react with urea to decompose it to water, carbon dioxide and nitrogen; nitric acid may precipitate it as white crystals of urea nitrate.