Effective plasma concentrations of itraconazole and its active metabolite for the treatment of pulmonary aspergillosis
| Autor: | Kana Matsumoto, Kunihiko Morita, Yaeko Nakamura, Atsuo Sato |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Microbiology (medical) medicine.medical_specialty Antifungal Agents Optimal cutoff Itraconazole 030106 microbiology Gastroenterology 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Pharmacology (medical) 030212 general & internal medicine Clinical efficacy Active metabolite Aged Retrospective Studies Aged 80 and over business.industry Mean age Middle Aged Pulmonary aspergillosis Treatment Outcome Infectious Diseases ROC Curve Plasma concentration Female Pulmonary Aspergillosis Once daily business medicine.drug |
| Zdroj: | Journal of Infection and Chemotherapy. 26:170-174 |
| ISSN: | 1341-321X |
| DOI: | 10.1016/j.jiac.2019.08.002 |
| Popis: | Background Itraconazole (ITCZ) is used to treat pulmonary aspergillosis, but findings regarding the range of effective plasma concentrations are often contradictory. This study attempted to determine effective plasma concentrations of ITCZ and its active metabolite hydroxyitraconazole (OH-ITCZ) by retrospectively analyzing their relationships to clinical efficacy. Methods The study included 34 patients with pulmonary aspergillosis treated using ITCZ (mean age, 70 years). Each patient was treated with 200 mg ITCZ once daily (mean duration of treatment: 384 days). Plasma concentrations of ITCZ and OH-ITCZ at trough levels from 7 to 889 days after the start of treatment were determined using high-performance liquid chromatography. Clinical efficacy was assessed through the improvement clinical symptoms. Results Fifteen patients were classified as effective group and the other 19 patients as non-effective group. Mean (±standard deviation) ITCZ trough plasma concentration was significantly higher in effective group (1254 ± 924 ng/mL) than in non-effective group (260 ± 296 ng/mL). Mean OH-ITCZ plasma concentration was significantly higher in effective group (1830 ± 1031 ng/mL) than in non-effective group (530 ± 592 ng/mL). Receiver operating characteristic curve analysis revealed the optimal cutoff for ITCZ trough plasma concentration was 517 ng/mL, and 86.7% of effective group showed concentrations exceeding this value. The optimal cutoff for total ITCZ + OH-ITCZ plasma concentration was 1025 ng/mL, and 93.3% of effective group showed a concentration exceeding this value. Conclusions Our findings indicate that effective plasma concentration ranges for the treatment of pulmonary aspergillosis begin at an ITCZ trough plasma concentration of 500 ng/mL and a total ITCZ + OH-ITCZ plasma concentration of 1000 ng/mL. |
| Databáze: | OpenAIRE |
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