Kinetic analysis of 5 sugar probes in dog serum after orogastric administration

Abstract

The objective of this study was to describe the kinetics of orally administered sugar probes in serum for the assessment of gastrointestinal permeability and intestinal absorptive capacity in dogs. Eight healthy dogs received lactulose (L), rhamnose (R), methylglucose (M), xylose (X), and sucrose (S) by orogastric intubation. Baseline blood samples and subsequently timed blood samples were taken during 24 hours. Sugars were analyzed by gas chromatography-mass spectrometry (GC-MS). Statistical analysis was performed using a Friedman test with Dunn's multiple comparison post test and a Kruskal-Wallis test. Statistical significance was set at a P-value < 0.05. Sugars in serum were detected after orogastric administration. Concentrations of L and R were significantly different from the baseline from 90 to 240 and 60 to 300 min, respectively, and those of X, M, and S were different from 30 to 240 min post-dosing (P < 0.05 for all 5 probes). Maximum concentrations of L and R were obtained at 180 min, while X, M, and S reached their maximum concentrations at 90 min post-dosing. For all sugars, no statistically significant differences were found between concentrations at 90, 120, and 180 min or between the coefficients of variation (CV%) of those mean concentrations for these 3 time points. Based on these data, the collection of 2 blood samples, one taken at baseline and the other obtained between 90 and 180 minutes after dosing, might be sufficient for the determination of gastrointestinal permeability and mucosal absorptive capacity using these 5 sugar probes in canine serum.

Figure 1

Representative total ion chromatogram. This figure shows a representative ion chromatogram for the 5 target sugar probes spiked in pooled canine serum samples at a concentration of 125 mg/L. Labeled peaks indicate major peaks of xylose (X), rhamnose (R), methylglucose (M), sucrose (S), lactulose (L), and the internal standard mannitol (m).

Figure 2

Concentration-time profile of lactulose [mean ± standard deviation (s)]. This figure shows the changes of lactulose concentrations in serum after orogastric administration in healthy dogs (n = 8). Serum concentrations of lactulose were significantly different from baseline at 90, 120, 180, 240 min post-dosing (P < 0.05), reaching the maximum peak concentration at 180 min post-dosing (mean ± s: 8.2 ± 4.9 mg/L).

Figure 3

Concentration-time profile of rhamnose [mean ± standard deviation (s)]. This figure shows the changes of rhamnose concentrations in serum after orogastric administration in healthy dogs (n = 8). Serum concentrations of rhamnose were significantly different from baseline at 60, 90, 120, 180, 240, and 300 min post-dosing (P < 0.05), reaching the maximum peak concentration at 180 min post-dosing (means ± s: 35.6 ± 4.4 mg/L).

Figure 4

Concentration-time profile of xylose [mean ± standard deviation (s)]. This figure shows the changes of xylose concentrations in serum after orogastric administration in healthy dogs (n = 8). Serum concentrations of xylose were significantly different from baseline at 30, 60, 90, 180, and 240 min post-dosing (P < 0.05), reaching the maximum peak concentration at 90 min post-dosing (means ± s: 224.0 ± 72.6 mg/L).

Figure 5

Concentration-time profile of methylglucose [mean ± standard deviation (s)]. This figure shows the changes of methylglucose concentrations in serum after orogastric administration in healthy dogs (n = 8). Serum concentrations of methylglucose were significantly different from baseline at 30, 60, 90, 120, 180, and 240 min post-dosing (P < 0.05), reaching the maximum peak concentration at 90 min post-dosing (means ± s: 214.8 ± 80.7 mg/L).

Figure 6

Concentration-time profile of sucrose [mean ± standard deviation (s)]. This figure shows the changes of sucrose concentrations in serum after orogastric administration in healthy dogs (n = 8). Serum concentrations of sucrose were significantly different from baseline at 30, 60, 90, 120, 180, and 240 min post-dosing (P < 0.05), reaching the maximum peak concentration at 90 min post-dosing (means ± s: 4.1 ± 1.7 mg/L).

Figure 7

Serum concentration-time curves of the 5 sugars after orogastric administration. Serum concentrations of xylose, rhamnose, and methylglucose are displayed on the y-axis on the left. Serum concentrations of lactulose and sucrose are displayed on the y-axis on the right. For all 5 sugars, no significant differences were found between concentrations measured at 90, 120, and 180 min time points or between the coefficients of variation (CV%) of the mean concentrations of these 3 points.