Intestinal Permeability and Role of P-Glycoprotein in Intestinal Absorption of Novel Triethylamine Containing Thiophene S006–830 Using Single-Pass Intestinal Perfusion in Rats

Figures & data

Figure 1. Chemical structures of S006–830 and 99–357(IS).

Figure 2. Chromatograms of S006-830.

(A) S006–830 chromatogram for extracted blank in intestinal perfusate, (B) S006–830 chromatogram for extracted quality control matrix sample, (C) extracted test sample.

Table 1. Recovery, accuracy and precision (intraday and interday) of S006–830.

QC standard	Nominal conc. (ng/ml)	Accuracy (%) (n = 3)		Precision (% RSD) (n = 3)		Percent recovery (mean ± SD)
		Intraday	Interday	Intraday	Interday
LQC	25	-0.60	-0.33	8.82	6.75	65.52 ± 2.34
MQC	400	-2.94	-4.89	4.75	5.33	61.87 ± 6.72
HQC	1600	-1.26	-1.41	2.50	2.96	65.39 ± 5.51

RSD: Relative standard deviation; QC: Quality check.

Table 2. P_eff values of S006–830 for duodenum, jejunum, ileum and duodenal (830+ Verapamil).

Time	Parameter	Duodenum	Jejunum	Ileum	830 + Ver	p-value duodenum vs 830+Ver
0–15	Mean Peff (×10^-3 cm/s)	72.5 ± 0.65	49.5 ± 1.50	47.4 ± 7.28	45.5 ± 7.07	0.0330
15–30		84.3 ± 5.17	72.9 ± 6.69	58.6 ± 14.11	55.2 ± 5.25	0.0305
30–60		77.0 ± 1.67	70.5 ± 4.48	66.0 ± 7.71	55.6 ± 3.56	0.165
60–90		93.8 ± 14.22	91.0 ± 4.48	69.3 ± 14.6	66.8 ± 12.99	0.155

Table 3. K_a values of S006–830 for duodenum, jejunum, ileum and duodenal (830+ Verapamil).

Time	Parameter	Duodenum	Jejunum	Ileum	830+Ver	p-value Duodenum vs 830+Ver
0–15		19.3 ± 0.01	18.4 ± 0.11	18.3 ± 0.49	13.8 ± 1.13	0.0211
15–30	Ka (×10^-2 min)	19.4 ± 0.04	19.2 ± 0.27	18.9 ± 0.26	15.8 ± 0.56	0.0119
30–60		19.4 ± 0.02	19.20.12	19.1 ± 0.16	16.3 ± 0.50	0.0261
60–90		19.5 ± 0.08	19.5 ± 0.13	19.2 ± 0.10	16.6 ± 0.55	0.0191

Table 4. Flux of phenol red concentration at different time point showing steady state at 10 cm intestine segment.

Time	Phenol red conc. (μg/ml)
0–15	50.61 ± 0.39
15–30	50.27 ± 5.73
30–60	45.66 ± 2.35
60–90	54.38 ± 0.23

Figure 3. Histological examination images of different intestinal segments after single pass perfusion study.

(A) Duodenum (B) jejunum (C) ileum, and (D) duodenal (S006–830 + verapamil).