TABLE 3.
Human pharmacokinetic data for the mold-active azole compoundsc
| Drug | Route or form of administration | Patient group (reference) | Dosage | Day(s) when steady state reached | Bioavailabilityd | Mean Cmax, mg/literd | Mean Cmin, mg/literd | Mean Cav, mg/literd | Mean total body CL/F (liters/h)d | Mean t1/2 (h)d | Mean AUC24 (mg · h/liter)d | Fraction unbound (%) | Mean V/F (liters/kg)d |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Isavuconazole | Oral or i.v. | Patients with IA (n = 222) (20) | 200 mg TID on days 1–2, 200 mg QD | 14 | 0.98–1 | 3.91 (49) | 2.4 (44) | 100 (50–150) | 97.9 (58) | 1 | >5 (44) | ||
| Posaconazole | Oral suspension | Febrile neutropenic patients or patients with refractory invasive fungal diseases (n = 23) (21) | 400 mg BID | 7–10 | 0.54–0.75 | 0.85 (82) | 0.64 (98) | 0.72 (86) [6.70–2,256] | 76.1 (78) [14.9–256] | 31.7 (42) [12.4–67.3] | 17.2 (86) [3.1–53.6] | 2 | 44 (84) [5.8–187] |
| Gastroresistant tablet (day 8) | Neutropenic patients receiving cytotoxic chemotherapy for AML or MDS (n = 32) (22) | 300 mg BID on day 1, 300 mg QD | 7–10 | 0.54–0.75 | 1.96 (33) | [0.343–2.55] | 1.46 (38) | 35 (41) [11.8–62.3] | |||||
| i.v. (day 14) | Neutropenic patients receiving cytotoxic chemotherapy for AML or MDS (n = 19) (23) | 300 mg BID on day 1, 300 mg QD | 1 | 2.61 (39) | 1.07 (50) | 1.43 (42) | 34.3 (42) | ||||||
| Voriconazole | Oral | Adult patients with IA (n = 43) (24) | 400 mg BID on day 1, 200 mg BID | 5–7 | 0.82 (15) | 3.57 (48.5)a | 0.83 (197) | 11.52 (73)a | 11.31 (87.3)a | 36 (119) | 2.6 (96) | ||
| Adult patients with proven or probable IA on combination therapy with anidulafungin (n = 454) (25) | 6 mg/kg of body wt BID on day 1, 4 mg/kg BID for 7 days, 300 mg BID | 5–7 | 0.64 (24) | 2.04 (54) | 5.30 (11) | 66 (45) | 45–55b | 2.38 (15–26) | |||||
| i.v. | Adult patients with IA (n = 43) (24) | 6 mg/kg BID on day 1, 4 mg/kg BID | 1 | 2.54 (231) | 90.4 (168) | 45–55b | 2.6 (96) | ||||||
| Adult patients with proven or probable IA on combination therapy with anidulafungin (n = 454) (25) | 6 mg/kg BID on day 1, 4 mg/kg BID | 1 | 3.10 (52) | 5.30 (11) | 102 (43) | 2.38 (15–26) |
a
Data obtained from reference 26.
b
Data obtained from reference 27.
c
Abbreviations: IA, invasive aspergillosis; AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; TID, three times daily; QD, once daily; BID, twice daily; Cmax, maximum concentration of drug in serum; Cmin, minimum concentration of drug in serum; Cav, average concentration of drug in serum; CL, clearance; F, bioavailability; t1/2, half-life; AUC24, area under the concentration-time curve at 24 h; V, volume of distribution.
d
Pharmacokinetic data in parentheses are percent coefficients of variation; data in brackets are ranges.