TABLE 2.
PK parameter values after twice-daily dosing of POS i.v. (day 1) and multiple doses of POS i.v. (day 14) administered to subjects at high risk for IFDa
| POS day of administration, cohort, and dosageb | No. of subjects | Cmax (mean [CV%c]) (ng/ml) | Tmax (median [range]) (h) | AUCd (mean [CV%]) (ng · h/ml) | Cavge (mean [CV%]) (ng/ml) | Cmin (mean [CV%]) (ng/ml) | Accumulation ratio (mean [CV%])f | Cavg of ≥500 and ≤2,500 ng/ml (%) |
|---|---|---|---|---|---|---|---|---|
| Day 1 | ||||||||
| Cohort 1: 200 mg b.i.d. | 20 | 990 (47) | 1.48 (1.0–4.0) | 5,390 (29) | NA | NA | NA | NA |
| Cohort 2: 300 mg b.i.d. | 22 | 1,590 (61) | 1.54 (1.0–2.0) | 8,240 (26) | NA | NA | NA | NA |
| Day 14 | ||||||||
| Cohort 1: 200 mg q.d. | 15 | 1,950 (50) | 1.00 (1.0–4.0) | 28,200 (51) | 1,180 (51) | 958 (63) | 3.6 (44) | 94 |
| Cohort 2: 300 mg q.d. | 19 | 2,610 (39) | 1.50 (0.98–4.0) | 34,300 (42) | 1,430 (42) | 1,068 (50) | 2.8 (31) | 95 |
a
i.v., intravenous; IFD, invasive fungal disease; POS, posaconazole; PK, pharmacokinetics; NA, not applicable.
b
b.i.d., twice daily; q.d., once daily.
c
CV, coefficient of variation; Cmax, maximum observed concentration; Tmax, time to Cmax; AUC, area under concentration-time curve; Cavg, average concentration at steady state; Cmin, minimum plasma concentration.
d
AUC from 0 to 12 h (AUC0–12 h) presented for day 1; AUC0–24 h presented for day 14.
e
Cavg = AUC0–24 h/dose interval, based on Cmax.
f
Accumulation ratio based on AUC0–24 h.