Table 3.

Comparison of Predicted and Observed Human Plasma Exposure after a Single 11-hour Infusion of ISIS 333611

Cohort	Dose (per 12 hr)	N	AUC (0-24hr) (hr*ng/mL)
			Mean (SE)	Median (range)	Predicted
1	0.15 mg	6	4.15 (2.93)	0 (0 - 19.9)	--
2	0.5 mg	6	0 (0)	0 (0 - 0)	--
3	1.5 mg	6	34.9 (10.3)	25.3 (12.3 - 77.6)	60.9
4	3.0 mg	6	77.6 (26.2)	62.1 (24.8 - 200)	122

AUC: Area under the curve calculated from individual measurements ofplasma from start of dosing through 12 hours after dosing.

Predicted A UC = Monkey A UCss24hr / (human body weight [70 kg]/monkey body weight [4 kg]) x (human dose [total mg]/monkey dose [mg/day]). Monkey AUC values are listed in Supplemental Table 2. Monkey A UC value at 0.1 mg/day was used for human calculations.