RESUMEN
A randomized, open-label, comparative study was conducted in 30 male patients with moderately advanced human immunodeficiency virus (HIV) infection to examine the pharmacokinetics of an investigational intravenous preparation of itraconazole compared with pharmacokinetics after administration of itraconazole capsules. The study also assessed whether adequate plasma concentrations of itraconazole could be rapidly achieved with the intravenous formulation and then maintained after cessation of intravenous therapy with itraconazole capsules. All patients received 200 mg intravenous itraconazole as a 1-hour infusion in 40% hydroxypropyl-beta-cyclodextrin (HP-beta-CD) vehicle twice daily for 2 days, and then 200 mg intravenously once daily for 5 days. Patients then received itraconazole capsules, either 200 mg twice daily or 200 mg once daily for 28 days. Steady-state plasma concentrations of itraconazole were reached by day 3 with intravenous infusion, a much shorter time than observed with administration of itraconazole capsules. Steady-state concentrations of itraconazole and hydroxyitraconazole were effectively maintained during the rest of the intravenous infusions of itraconazole. Oral follow-up with administration of 200-mg capsules once daily could not maintain the plasma concentrations of itraconazole and hydroxyitraconazole obtained at the end of the intravenous treatment, whereas twice-daily oral administration maintained or increased these concentrations. Mean plasma concentrations of itraconazole and hydroxyitraconazole on day 7 were similar to those on day 36 in the twice-daily group. Mean renal clearance was comparable to mean total body clearance, and approximately 93% to 101% of the HP-beta-CD was excreted unchanged in urine within 12 hours of administration. The HP-beta-CD was essentially eliminated through the kidney, and little accumulation in the body was observed in this patient population. Adverse events during the intravenous phase were most commonly associated with intravenous administration. Intravenous infusion of itraconazole for 7 days followed by administration of itraconazole capsules twice daily for 28 days is an effective dose regimen in patients with advanced HIV infection.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/metabolismo , Antifúngicos/farmacocinética , Itraconazol/farmacocinética , beta-Ciclodextrinas , 2-Hidroxipropil-beta-Ciclodextrina , Administración Oral , Adulto , Anciano , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Antifúngicos/sangre , Ciclodextrinas/sangre , Ciclodextrinas/farmacocinética , Ciclodextrinas/orina , Femenino , Humanos , Inyecciones Intravenosas , Itraconazol/administración & dosificación , Itraconazol/efectos adversos , Itraconazol/análogos & derivados , Itraconazol/sangre , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To assess handwritten medication orders for legibility and completeness, legibility of physician signatures, and presence of date and time the orders were written. DESIGN: Descriptive. SETTING: Three patient care units in one hospital in Texas. SAMPLE: One hundred seventy-six medication orders and 55 signatures by 36 different physicians for 39 patients. METHODS: Six experienced nurses evaluated medication orders and signatures for legibility using a rating scale developed for the study. Completeness of medication orders and presence of date and time were determined. RESULTS: Twenty percent [corrected] of the medication orders and 78% of the signatures were illegible or legible with effort. Twenty-four percent of the medication orders were incomplete. Date was omitted on 18% of the medication orders, and time was missing on 58%. CONCLUSION: Difficult-to-read and incomplete medication orders continue to be an important system problem that can increase risk for medication errors and patient harm. Good penmanship and complete orders are unrealistic goals without system support.