TABLE 2.

Mean values of pharmacokinetic parameters

TreatmentCmax (ng/ml)AUC (ng·h/ml)aTmaxb (h)CL/F (liters/h)t1/2 (h)V/F (liters)
Part 1: effect of gastric pH (nc = 12)
    Posaconazole 400 mg SDd151 (58)e5,600 (53)5 (3-6)83.6 (51)27.4 (22)3,330 (53)
    Posaconazole 400 mg SD + acidic carbonated beverage286 (55)9,610 (49)4 (3-6)52.2 (57)25.2 (16)1,840 (50)
    Posaconazole 400 mg SD + PPI76.7 (37)3,700 (41)6 (4-6)116 (42)25.7 (15)4,350 (51)
    Posaconazole 400 mg SD + PPI + acidic carbonated beverage93.3 (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)f982 (62)52,300 (89)6 (3-12)54.6 (71)25.7 (23)NRg
    Posaconazole 400 mg BID + nutritional supplement (7 days)f1,590 (61)80,600 (73)h6 (0-8)33.9 (58)h29.5 (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)f2,160 (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 fasted181 (106)4,280 (44)5 (3-8)110 (62)24.5 (26)3,580 (39)
    Posaconazole 400 mg SD before meal274 (70)10,000 (68)7 (4-12)57.4 (63)23.9 (21)1,900 (55)
    Posaconazole 400 mg SD during meal555 (44)20,900 (49)8 (5-12)24.3 (58)22.8 (29)793 (67)
    Posaconazole 400 mg SD after meal544 (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)i24.3 (15)i1,660 (24)i
    Posaconazole 400 mg SD + nutritional supplement + metoclopramide (n = 13)232 (32)7,390 (45)5 (4-6)59.6 (43)j27.7 (29)j2,280 (42)j
    Posaconazole 400 mg SD + nutritional supplement + loperamide (n = 12)294 (42)10,400 (54)5 (4-6)44.6 (43)k27.5 (11)k1,750 (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.