Hydroxy-itraconazole pharmacokinetics is similar to that of itraconazole in immunocompromised patients receiving oral solution of itraconazole
| Autor: | Takayuki Watanabe, Hiroshi Yamada, Tatsuya Yagi, Yasuaki Mino, Takahiro Yamada, Takafumi Naito, Junichi Kawakami |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Antifungal Agents Itraconazole Metabolite Clinical Biochemistry Serum albumin Administration Oral Renal function Pharmacology Biochemistry Drug Administration Schedule Immunocompromised Host chemistry.chemical_compound Pharmacokinetics Tandem Mass Spectrometry medicine Humans Serum Albumin Active metabolite Aged biology Biochemistry (medical) Albumin General Medicine Middle Aged Solutions Mycoses chemistry Hematologic Neoplasms Plasma concentration biology.protein Female Chromatography Liquid Glomerular Filtration Rate Immunoproliferative Disorders medicine.drug |
| Zdroj: | Clinica Chimica Acta. 415:128-132 |
| ISSN: | 0009-8981 |
| DOI: | 10.1016/j.cca.2012.10.028 |
| Popis: | The pharmacokinetic variability of hydroxy-itraconazole (OH-ITZ), an active metabolite of itraconazole (ITZ), is not fully known.Oral solution of ITZ was administered in 46 immunocompromised patients as a single 200 mg dose for at least 12 days. The plasma concentrations of ITZ, active OH-ITZ, and keto-itraconazole (keto-ITZ), an inactive metabolite, 12 h after administration were determined by LC-UV or LC-MS/MS.The mean±SD of plasma concentrations of ITZ, OH-ITZ, and keto-ITZ were 833±468, 798±454, and 3.94±2.68 μg/l, respectively. A greater correlation coefficient was observed between plasma concentrations of ITZ and OH-ITZ (r=0.90, P0.01) than between OH-ITZ and keto-ITZ (r=0.44, P0.01). Plasma concentration of OH-ITZ was inversely correlated with concentration ratio of keto-ITZ to OH-ITZ (r=-0.52, P0.01). Plasma concentrations of ITZ and OH-ITZ were correlated with serum concentration of albumin (r=0.36, P=0.01 and r=0.37, P=0.01) and estimated glomerular filtration rate (r=-0.27, P=0.08 and r=-0.35, P=0.02).The pharmacokinetic variability of OH-ITZ was associated with saturated metabolism to keto-ITZ, serum concentration of albumin, and renal function in immunocompromised patients. The plasma concentration of OH-ITZ was strongly correlated with that of ITZ. Prevention of fungal infections can be improved by determining the plasma concentration of ITZ or OH-ITZ. |
| Databáze: | OpenAIRE |
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