Clinical significance of measuring the blood concentration of itraconazole oral solution in the field of hematology.
Some studies indicated that preventive therapy with Itraconazole oral solution (ITCZ-OS) significantly decreased the incidence of invasive fungal infection, whereas others emphasized that there was no significant decrease. On the other hand, a study involving patients with neutropenia showed a 15-fold increase in the blood concentration of Itraconazole (ITCZ). Therefore, when administering ITCZ-OS, which is more rapidly absorbed in the digestive tract compared to its conventional dosage forms, to patients with blood disease, the blood concentration of ITCZ should be measured to maintain its efficacy and safety. To promote the appropriate use of ITCZ-OS, we conducted blood drug concentration monitoring, and investigated its clinical significance. The subjects were 26 patients with blood diseases. The blood level of ITCZ was measured using HPLC. The mean blood level of ITCZ was 2396.5±1742.7 ng/ml (mean±S.D.). The mean blood level of hydroxy-ITCZ was 5384.4±3348.2 ng/ml. The dose was not correlated with the blood levels of ITCZ/hydroxy-ITCZ per body weight (R(2)=0.134, 0.154, p=0.094, 0.071). Furthermore, the blood levels of ITCZ and hydroxy-ITCZ per body weight were significantly higher in females (p=0.025, 0.010). In males, there was a correlation between the creatinine clearance and blood level of ITCZ per body weight (R(2)=0.319, p=0.044). The blood levels of ITCZ varied among the patients. In addition, when ITCZ-OS was administered at a daily dose of 200 mg (ITCZ), the blood levels of ITCZ exceeded a trough level at which this agent may be effective in patients with febrile neutropenia in whom fungal infection is suspected.
Pharmaceutical Health Care and Sciences, Tokyo University of Pharmacy and Life Science, 1432–1 Horinouchi, Hachiouji, Tokyo 192–0392, Japan. shimoeda@toyaku.ac.jp
Sadahiko
S
Shimoeda
Saori
S
Nakagawa
Hikaru
H
Kobayashi
Susumu
S
Yamato
Kenji
K
Kawano
Shin
S
Ohta
D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D005260:Female; D006402:Hematologic Diseases / Q000188:drug therapy; D006405:Hematology / Q000379:methods; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage* / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009181:Mycoses; D009503:Neutropenia / Q000188:drug therapy; D012737:Sex Factors; D012996:Solutions
D000935:Antifungal Agents; D012996:Solutions; D017964:Itraconazole; D003404:Creatinine