Monitoring Amphotericin B and Fluconazole Concentrations in the Plasma and Cerebrospinal Fluid of Patients with Cryptococcal Meningitis

Monitoring Amphotericin B and Fluconazole Concentrations in the Plasma and Cerebrospinal Fluid of Patients with Cryptococcal Meningitis

Objectives: To determine whether amphotericin B (AmB) and fluconazole cross the blood-brain barrier in a similar manner in patients with HIV-associated cryptococcal meningitis based on the cerebrospinal fluid (CSF)/plasma drug ratio through a comparative study. Methods: This prospective, open-label...

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Bibliographic Details
Main Authors: Sílvia Regina Cavani Jorge Santos, Mara Cristina da Silva Martins Pappalardo, Grazziela Samantha Perez, Cristina Sanches-Giraud, Márcia de Souza Carvalho Melhem
Format: Article
Language:English
Published: Formifarma, LDA. 2012-10-01
Series:Revista Portuguesa de Farmacoterapia
Subjects:
open-label clinical protocol included 21 male and female patients
28-55 years of age. The patients were infected with HIV (CD4 50-200 cells/mL) and cryptococcal meningitis and were receiving AmB (1 mg/kg daily
infusion of four hours; 6-10 weeks) and fluconazole (400 mg 12 qh; until CSF was negative for fungal growth). The patients were informed in detail about all procedures to be performed in the hospital
including blood and CSF sample collection
if required. The study protocol was approved by the hospital’s ethical committee. Plasma samples were obtained by centrifugation at 2800 g for 30 min
and CSF samples were collected by the physician to relieve symptoms caused by intracranial hypertension. The drug concentrations of both antifungal agents were determined in the biological samples using HPLC. Results: The mean drug plasma: CSF concentrations were 2.30:0.3 μg/mL and 31.7:19.4 μg/mL for AmB and fluconazole
respectively. The CSF:plasma ratios were 0.20 (AmB) and 0.67 (fluconazole). Conclusions: Unlike fluconazole
the conventional AmB formulation did not reach the optimum CSF drug concentration. However
Amphotericin B
fluconazole
cerebrospinal fluid/plasma ratio
HIV infection and cryptococcal meningitis
Online Access:http://revista.farmacoterapia.pt/index.php/rpf/article/view/61

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