TABLE 2

Estimated drug exposure for the intravital imaging studies

Exposure of AMG-009 or bosentan during the intravital imaging studies, and an estimated C_max based on previously conducted intravenous studies with these compounds. As shown, subject number 1 in the 3 mg/kg bosentan dose group had no measurable exposure (limit of quantitation was 100 µg/l). Given that the other two animals in this dose group had plasma concentrations 13–36 times the limit of quantitation, it was concluded that subject number 1 was not properly dosed and imaging data for this animal was removed from the data set. The formula weight for AMG-009 is 581.47 and for bosentan is 551.62.

Compound Dose	Fluorescent Probe	Subject	Plasma	Estimated C_max	Estimated C_max	Mean Estimated C_max
			µg/l	µg/l	µM	µM
AMG-009
3 mg/kg	CGamF	8	1970	3500	6	11
		9	3240	5700	10
		10	5280	9200	16
10 mg/kg	CGamF	11	28,600	50,000	86	74
		12	25,000	44,000	76
		13	20,200	35,000	60
30 mg/kg	CGamF	14	120,000	210,000	360	510
		15	191,000	330,000	570
		16	195,000	340,000	590
30 mg/kg	CLF	17	177,000	310,000	530	430
		18	135,000	240,000	410
		19	115,000	200,000	350
Bosentan
3 mg/kg	CGamF	1	BQL	—	—	6.3
		2	1340	1900	3.4
		3	3650	5100	9.2
10 mg/kg^{^a}	CGamF	4	15,700	22,000	40	37
	CGamF	5	13,800	19,000	34	37
30 mg/kg^{^a}	CGamF	6	41,100	58,000	110	170
	CGamF	7	86,700	120,000	220	170
30 mg/kg	CLF	20	59,800	84,000	150	210
		21	101,000	140,000	250
		22	88,400	120,000	220

BQL, below the quantitation limit.
↵^a Blood was not collected for exposure analysis for one animal in each of the 10 and 30 mg/kg bosentan groups.