Table 5.

a Toxicokinetic parameters for MRx102 following a single i.v. dose of MRx102 and following seven consecutive daily i.v. doses of MRx102 in dogs
Group	Day	Sex	Dog #	Dose (mg/kg/day)	C0 (ng/ml)	Cmax (ng/ml)	Tmax (hr)	AUC0–24hr (ng*hr/ml)	AUC0-inf (ng*hr/ml)	T1/2,e (hr)	Cl (l/hr)	Vz (l)
2	1	F	35	0.1	23.6	9.90	0.25	8.26	8.11	0.31	12.3	5.4
2	1	F	38	0.1	24.5	9.29	0.25	7.86	7.72	0.30	13.0	5.7
2	1	M	25	0.1	17.1	8.82	0.25	19.99	9.015	0.79	11.1	12.7
2	1	M	29	0.1	15.8	7.79	0.25	6.68	6.67	0.36	15.0	7.8
3	1	F	36	0.3	50.6	26.0	0.25	49.17	24.08	0.67	12.5	12.1
3	1	F	39	0.3	46.9	26.1	0.25	51.39	28.47	0.63	11.8	10.6
3	1	M	28	0.3	110	58.1	0.25	103.9	53.60	0.60	5.6	4.9
3	1	M	30	0.3	69.8	32.0	0.25	67.55	31.28	0.83	9.6	11.5
4	1	F	33	1.0	163	90.8	0.25	144.1	78.27	0.55	12.8	10.0
4	1	F	37	1.0	283	153	0.25	214.5	214.5	0.43	4.7	2.9
4	1	M	26	1.0	260	113	0.25	139.6	94.98	0.44	10.5	6.7
4	1	M	27	1.0	139	86.6	0.25	169.7	169.8	0.51	5.9	4.4
2	7	F	35	0.1	10.8	6.07	0.25	5.63	5.96	0.48	16.8	11.7
2	7	F	38	0.1	5.01	4.38	0.25	3.96	4.01	0.36	25.0	12.6
2	7	M	25	0.1	18.6	12.3	0.25	27.95	12.64	0.66	7.9	7.5
2	7	M	29	0.1	12.3	6.88	0.25	5.76	5.72	0.33	17.5	8.3
3	7	F	36	0.3	35.0	22.3	0.25	62.95	62.95	0.71	4.8	4.9
3	7	F	39	0.3	50.9	26.3	0.25	45.91	25.15	0.56	11.9	9.6
3	7	M	28	0.3	140	59.6	0.25	146.7	47.59	0.28	6.3	2.6
3	7	M	30	0.3	67.0	28.6	0.25	55.51	28.16	0.73	10.6	11.2
4	7	F	33	1.0	317	167	0.25	301.2	301.2	0.56	3.3	2.7
4	7	F	37	1.0	a	a	a	a	a	a	a	a
4	7	M	26	1.0	218	118	0.25	237.6	237.6	0.58	4.2	3.5
4	7	M	27	1.0	985	593	0.25	554.0	579.6	0.47	1.7	1.2

b Toxicokinetic parameters for triptolide following a single i.v. dose of MRx102 and following seven consecutive daily i.v. doses of MRx102 in dogs
Group	Day	Sex	Dog #	Dose (mg/kg/day)	Cmax (ng/ml)	Tmax (hr)	AUC0–24hr (ng*hr/ml)	AUC0-inf (ng*hr/ml)	T1/2,e (hr)
2	1	F	35	0.1	a	a	a	a	a
2	1	F	38	0.1	a	a	a	a	a
2	1	M	25	0.1	2.22	2	25.53	c	c
2	1	M	29	0.1	a	a	a	a	a
3	1	F	36	0.3	2.00	1	1.5	c	c
3	1	F	39	0.3	2.74	2	33.54	c	c
3	1	M	28	0.3	2.85	2	34.83	c	c
3	1	M	30	0.3	2.34	2	26.91	c	c
4	1	F	33	1.0	8.35	1	95.13	c	c
4	1	F	37	1.0	8.76	2	212.2	c	c
4	1	M	26	1.0	113	1	89.11	c	c
4	1	M	27	1.0	9.16	2	114.7	c	c
2	7	F	35	0.1	a	a	a	a	a
2	7	F	38	0.1	a	a	a	a	a
2	7	M	25	0.1	a	a	a	a	a
2	7	M	29	0.1	a	a	a	a	a
3	7	F	36	0.3	3.15	2	38.09	c	c
3	7	F	39	0.3	3.71	1	40.03	c	c
3	7	M	28	0.3	3.74	1	44.96	c	c
3	7	M	30	0.3	3.17	2	38.65	c	c
4	7	F	33	1.0	21.1	0.25	301.2	c	c
4	7	F	37	1.0	b	b	b	b	b
4	7	M	26	1.0	13.4	1	124.0	c	c
4	7	M	27	1.0	49.0	1	78.28	c	c

^aCould not be calculated or determined; animal found dead after dosing on Day 7.

^aAll designated samples were BLQ for triptolide

^bCould not be calculated or determined; animals found dead after dosing on Day 7

^cCould not be calculated or determined

^dAUC_0–24hr - area under the curve from time zero to 24 hours