TABLE 2.
Mean values of pharmacokinetic parameters
| Treatment | Cmax (ng/ml) | AUC (ng·h/ml)a | Tmaxb (h) | CL/F (liters/h) | t1/2 (h) | V/F (liters) |
|---|---|---|---|---|---|---|
| Part 1: effect of gastric pH (nc = 12) | ||||||
| Posaconazole 400 mg SDd | 151 (58)e | 5,600 (53) | 5 (3-6) | 83.6 (51) | 27.4 (22) | 3,330 (53) |
| Posaconazole 400 mg SD + acidic carbonated beverage | 286 (55) | 9,610 (49) | 4 (3-6) | 52.2 (57) | 25.2 (16) | 1,840 (50) |
| Posaconazole 400 mg SD + PPI | 76.7 (37) | 3,700 (41) | 6 (4-6) | 116 (42) | 25.7 (15) | 4,350 (51) |
| Posaconazole 400 mg SD + PPI + acidic carbonated beverage | 93.3 (34) | 4,180 (35) | 6 (4-12) | 97.4 (33) | 27.8 (36) | 3,920 (48) |
| Part 2: effect of dosing regimen (BID/QID) and prandial state (n = 12) | ||||||
| Posaconazole 400 mg BID alone (7 days)f | 982 (62) | 52,300 (89) | 6 (3-12) | 54.6 (71) | 25.7 (23) | NRg |
| Posaconazole 400 mg BID + nutritional supplement (7 days)f | 1,590 (61) | 80,600 (73)h | 6 (0-8) | 33.9 (58)h | 29.5 (28) | NR |
| Posaconazole 200 mg QID alone (7 days) | 2,300 (44) | 132,000 (54) | 4 (0-6) | 21.2 (71) | 34.7 (39) | NR |
| Posaconazole 200 mg QID + nutritional supplement (7 days)f | 2,160 (44) | 112,000 (49) | 4 (0-5) | 20.4 (53) | 27.8 (41) | NR |
| Part 3: effect of food and meal timing relative to dose (n = 12) | ||||||
| Posaconazole 400 mg SD fasted | 181 (106) | 4,280 (44) | 5 (3-8) | 110 (62) | 24.5 (26) | 3,580 (39) |
| Posaconazole 400 mg SD before meal | 274 (70) | 10,000 (68) | 7 (4-12) | 57.4 (63) | 23.9 (21) | 1,900 (55) |
| Posaconazole 400 mg SD during meal | 555 (44) | 20,900 (49) | 8 (5-12) | 24.3 (58) | 22.8 (29) | 793 (67) |
| Posaconazole 400 mg SD after meal | 544 (50) | 21,000 (48) | 6 (5-12) | 23.7 (54) | 22.6 (28) | 757 (51) |
| Part 4: effect of gastric motility (n = 13) | ||||||
| Posaconazole 400 mg SD + nutritional supplement (n = 12) | 303 (40) | 8,960 (42) | 5.5 (5-6) | 49.4 (34)i | 24.3 (15)i | 1,660 (24)i |
| Posaconazole 400 mg SD + nutritional supplement + metoclopramide (n = 13) | 232 (32) | 7,390 (45) | 5 (4-6) | 59.6 (43)j | 27.7 (29)j | 2,280 (42)j |
| Posaconazole 400 mg SD + nutritional supplement + loperamide (n = 12) | 294 (42) | 10,400 (54) | 5 (4-6) | 44.6 (43)k | 27.5 (11)k | 1,750 (41)k |
a
AUC to final measurable sampling time.
b
Values are medians (ranges).
c
n, number of subjects.
d
SD, single dose.
e
Unless indicated otherwise, values in parentheses are percent CV.
f
n = 11; no concentration data were available for one subject.
g
NR, not reported.
h
n = 10; no concentration data were available for one subject; the predose concentration was missing for one subject.
i
n = 9; pharmacokinetic parameters for three subjects were excluded due to extrapolated area of >25% of total AUC.
j
n = 12; pharmacokinetic parameters for one subject were excluded due to extrapolated area of >25% of total AUC.
k
n = 11; pharmacokinetic parameters for one subject were excluded due to extrapolated area of >25% of total AUC.