Effective plasma concentrations of itraconazole and its active metabolite for the treatment of pulmonary aspergillosis期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

Effective plasma concentrations of itraconazole and its active metabolite for the treatment of pulmonary aspergillosis

Affiliation:	1. Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women''s College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan;2. Department of Pharmacy, National Hospital Organization, Minami-Kyoto Hospital, Jyoyo, Kyoto 610-0113, Japan;3. Department of Respiratory, National Hospital Organization, Minami-Kyoto Hospital, Jyoyo, Kyoto 610-0113, Japan;1. Department of Internal Medicine & Infectious Diseases, University Hospital of Heraklion, School of Medicine, University of Crete, 71110 Voutes, Heraklion, Crete, Greece;2. Department of Clinical Microbiology, University Hospital of Heraklion, School of Medicine, University of Crete, 71110 Voutes, Heraklion, Crete, Greece;3. National Reference Laboratory for Staphylococci, Department of Microbiology, School of Medicine, University of Patras, Patras, Greece;1. Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan;2. Department of General Internal Medicine, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan;3. Department of Pediatrics, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan;1. Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan;2. Department of Infectious Diseases, Mie University Hospital, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan;3. Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan;4. Clinical Laboratories, Mie University Hospital, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan;5. Department of Neurology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan;1. Departamento de Enfermedades Infecciosas, Hospital de Infectología, Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social, IMSS, Mexico City, Mexico;2. Departamento de Microbiología, Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, IPN, Mexico City, Mexico;3. Centro de Simulación Médica, Facultad Mexicana de Medicina, Universidad La Salle, Mexico City, Mexico;4. Laboratorio Central de Epidemiología, División de Laboratorios de Vigilancia e Investigación Epidemiológica, CMN “La Raza”, Instituto Mexicano del Seguro Social, IMSS, Mexico City, Mexico;5. Unidad de Investigación en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, IMSS, Mexico City, Mexico;6. Departamento de Patología Clínica, Banco Central de Sangre, CMN “La Raza”, Instituto Mexicano del Seguro Social, IMSS, Mexico City, Mexico;7. Laboratorio de Urgencias, Hospital de Infectología, Instituto Mexicano del Seguro Social, IMSS, Mexico City, Mexico;8. Center for HIV and Hepatogastroenterology, Duesseldorf, Germany;1. Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan;2. Diagnostic Center for Animal Health and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan;3. Division of Clinical Research, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba, 260-8673, Japan;4. Department of Medical Technologist, Obihiro-Kosei General Hospital, West 14 South 10-1, Obihiro, Hokkaido, 080-0016, Japan;5. Department of Nutrition Science, University of Nagasaki, Nagasaki, Japan;6. Division of Bio-resources, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba, 260-8673, Japan;1. Department of Pharmacy Practice, College of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia;2. Pharmacy Practice and Science Department, College of Pharmacy, University of Arizona, Tucson, AZ, USA

Abstract:	BackgroundItraconazole (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.MethodsThe 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.ResultsFifteen 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.ConclusionsOur 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.

Keywords:	Itraconazole Hydroxyitraconazole Pulmonary aspergillosis Plasma concentration Clinical efficacy Receiver operating characteristic curve analysis
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