Plasma concentration of itraconazole in patients receiving chemotherapy for hematological malignancies: the effect of famotidine on the absorption of itraconazole.
Fungal infection is a serious complication in immunocompromised patients, especially those with neutropenia. Itraconazole (ITZ) is expected to be an effective prophylactic agent for fungal infection because it has more activity against Aspergillus species than fluconazole and it is less toxic than amphotericin-B. However, ITZ is available only as an oral capsule, the absorption of which is thought to depend on the presence of acid in the stomach. In this study, the effect of famotidine, an H2-blocker, on the absorption of ITZ was investigated. Patients undergoing chemotherapy for hematological malignancies were enrolled. To minimize the effect of famotidine, the time of ITZ intake was different from that of famotidine intake. The plasma concentrations of ITZ with or without taking famotidine were determined just before and 4 h after ITZ intake. Mean trough and peak concentrations of ITZ without famotidine were 332 ng/ml and 476 ng/ml, respectively. When famotidine was co-administered, the concentrations decreased to 204 ng/ml and 315 ng/ml, respectively. Statistical analyses revealed significant differences between trough concentrations in the presence and absence of famotidine (p = 0.008). There was also a clear tendency toward higher peak concentrations in the plasma concentrations with famotidine (p = 0.06). These findings suggest that famotidine decreases the plasma concentration of ITZ in patients undergoing chemotherapy. Close monitoring of the plasma concentration of ITZ and dose adjustment are required for efficient prophylaxis.
Kanda
Y
Y
Department of Cell Therapy and Transplantation Medicine, Faculty of Medicine, University of Tokyo, Japan.
Kami
M
M
Matsuyama
T
T
Mitani
K
K
Chiba
S
S
Yazaki
Y
Y
Hirai
H
H
D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D015738:Famotidine / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D016867:Immunocompromised Host; D007408:Intestinal Absorption / Q000187:drug effects; D017964:Itraconazole / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000935:Antifungal Agents; D006635:Histamine H2 Antagonists; D017964:Itraconazole; D015738:Famotidine