The metabolic fate of doubly labelled lactose-(13C, 15N)ureide after pre-dosing with different ureides.

摘要

BACKGROUND: To date, the measurement of the orocaecal transit time (OCTT) with lactose-[(13)C]ureide usually requires a pre-dosing with the analogous substrate in its unlabelled form. OBJECTIVE: In this study, the enzyme induction provoked by different unlabelled sugar ureides in OCTT measurements when using doubly labelled lactose-[(13)C, (15)N]ureide (DLLU) was evaluated. METHODS: Thirteen healthy adults (age: 22-58 years) received 500 mg DLLU together with a standardized breakfast. Expired air, urine and faeces were collected over a period of 14, 48 and 72 h, respectively. After 1 and 2 weeks, the test was repeated after pre-dosing of 3 x 120 mg glucose ureide (GU) and 3 x 200 mg cellobiose ureide (CU), respectively, on the day before study begin. The (13)C- and (15)N-enrichments were measured by isotope ratio mass spectrometry. The OCTT was calculated by the detection of a significant (13)CO(2) increase. RESULTS: In comparison with the period without pre-dosing (7.8+/-2.2 h), the measured OCTT was significantly lowered either after GU pre-dosing (5.8+/-1.9 h, P=0.033) or CU pre-dosing (6.0+/-2.2 h, P=0.039). The respective renal (13)C- and (15)N-excretions amounted to 24.5 and 45.6, 24.7 and 54.0, and 22.5 and 50.1%, respectively, whereas the faecal (13)C- and (15)N-excretions amounted to 12.1 and 45.8, 4.8 and 21.5, and 9.6 and 39.8%, respectively. CONCLUSIONS: Pre-dosing with unlabelled GU and CU before the administration of DLLU led to an unequivocal induction of the enzyme activity and resulted in a definitive estimation of the OCTT, clearly demonstrating that glucose-[(13)C]ureide is the matrix of the bacterial degradation in the caecum.