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. 2021 Mar 18;65(4):e02479-20. doi: 10.1128/AAC.02479-20

TABLE 2.

Plasma pharmacokinetic parameters in NHPs after oral administration of AT-527a

Compound Cmaxb (μM) C12c (μM) Tmaxd (h) t1/2 (h) AUC0–12e (μM·h)
AT-511 (parent prodrug) 0.64 ± 0.08 ND 0.5–1 0.7 0.44 ± 0.09
AT-551 (intermediate prodrug) 0.68 ± 0.25 0.20 ± 0.07 1–4 8.8 4.35 ± 1.77
AT-273 (plasma surrogate for intracellular TP) 0.16 ± 0.02 0.10 ± 0.01 2 16 1.56 ± 0.18
a

Nonhuman primates (NHPs) were given a loading dose of 60 mg/kg AT-527, followed by five doses of 30 mg/kg every 12 h. Plasma samples were collected prior to the 5th dose and then 0.5, 1, 2, 4, 6, 8, 12 (preceding the 6th dose), and 14 h thereafter and analyzed for AT-511 and its metabolites by LC-MS/MS. Data are expressed as means ± SEs (n = 3). ND, not detected. The analytes in the putative metabolic pathway for AT-527 are shown in Fig. 1.

b

Cmax, maximum concentration across the time points measured.

c

C12, concentration at 12 h.

d

Tmax, time at which Cmax was observed.

e

AUC0–12, area under the plasma concentration versus time curve, from 0 to 12 h.

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