Reaction of sulphamethoxazole in bactrim DS with carbohydrates to form glucosylamines in vitro and in vivo

Abstract Sulphamethoxazole (SMX) reacts with glucose under mildly acidic conditions to reversibly form glucosylamines. Dissolution tests in 0.1 M hydrochloric acid containing 5% (w/v) glucose and a variety of other beverages containing reducing carbohydrates result in the formation of 20–30% glucosylamines and other carbohydrate conjugates during the dissolution process. Co-administration of 15 g of glucose did not significantly alter peak concentration, time of peak and area under the plasma concentration-time curve (0–36 h) for SMX, N-acetylsulphamethoxazole or trimethoprim (TMP) in a 2-way cross-over comparison in human volunteers given Bactrim DS® (SMX, 800 mg and TMP, 160 mg) orally. The co-administration of glucose reduced the absorption rate constant ( k a ) for SMX ( P =0.027) but not that for TMP. The data suggest that glucosylamines of SMX are readily formed in the presence of glucose in vitro and probably also in vivo in the stomach. However, formation is reversible and the glucosylamines have only a minor influence on k a and no significant effect on SMX bioavailability.