Table S1.

Rabbit plasma exposure of SB568859 and plasma Lp-PLA₂ activity at days 4, 5, and 6 and following administration of 3–30 mg⋅kg⁻¹⋅d⁻¹ SB568859 by oral gavage

Group (n = 6–8)	Day 4		Day 5		Day 6
	PK, ng/mL*	Lp-PLA2 activity†	PK, ng/mL*	Lp-PLA2 activity†	PK, ng/mL*	Lp-PLA2 activity†
Vehicle PO BID‡	BLQ	20.78 ± 0.57	BLQ	18.90 ± 0.43	BLQ	20.40 ± 0.72
SB568859 3 mg/kg PO BID	31.21 ± 3.84	13.95 ± 0.95	27.85 ± 1.71	13.28 ± 0.46	34.87 ± 3.62	12.24 ± 1.33‡
SB568859 10 mg/kg PO BID	48.93 ± 1.88	6.01 ± 0.62	47.76 ± 3.32	5.61 ± 0.39‡	47.55 ± 2.25	3.71 ± 0.41
SB568859 30 mg/kg PO BID	69.79 ± 7.27	3.01 ± 0.36‡	59.60 ± 5.72	2.59 ± 0.27‡	68.10 ± 5.94	1.58 ± 0.19
Kenacort IVT	—	—	—	—	BLQ	21.65 ± 0.72

Male HY79b-pigmented rabbits were treated with SB568859 administered by mouth, at 0 (vehicle alone, n = 6), 3 (n = 6), 10 (n = 8), and 30 mg/kg, respectively, (n = 8) at each dose, once on day 1, twice (8 AM and 4 PM) on days 2–5, and once on day 6. Blood samples were collected on day 4 and day 5 (before the scheduled SB568859 dosing, equivalent to C_trough), and on day 6 (∼2–3 h after the day 6 SB568859 dosing) for determination of SB568859 concentration and Lp-PLA₂ enzyme activity. Plasma was prepared by centrifugation at 13,000 x g and stored at −80 °C. SB568859 concentration was measured following protein precipitation by HPLC/MS/MS analysis. Lp-PLA₂ activity was evaluated by determining the enzyme-catalyzed release of [³H-] acetate from 1-O-hexadecyl-2-O-[³H-]acetyl-sn-glycer-3-phophorylcholine. BLQ, below level of quantitation; PO BID, by mouth, twice a day.

^*ng SB568859/ml rabbit plasma, mean ± standard deviation of the mean.

^†Lp-PLA2 enzyme rate (nmol/min/mL), mean ± standard deviation of the mean.

^‡Indicates n = 7.