Minimum concentration of Amphotericin B in serum according to the formulation, dose, and daily or prolonged intermittent therapeutic regimen

Abstract

Introduction: The therapeutic efficacy of daily amphotericin B infusion is related to its maximum concentration in blood; however, trough levels may be useful in intermittent regimens of this antifungal drug. Methods: High performance liquid chromatography (HPLC) was used to determine the minimum concentration (Cmin) of amphotericin B in the serum of patients receiving deoxycholate (D-Amph) or liposomal amphotericin B (L-AmB) for the treatment of cryptococcal meningitis (n=28), histoplasmosis (n=8), paracoccidioidomycosis (n=1), and leishmaniasis (n=1). Results: Daily use of D-Amph 30 to 50 mg or LAmB 50 mg resulted in a similar Cmin, but a significant increase ocurred with LAmB 100 mg/day. The geometric mean Cmin tended to decrease with a reduction in the dose and frequency of intermittent LAmB infusions: 357 ng/mL (100 mg 4 to 5 times/week) > 263 ng/mL (50 mg 4 to 5 times/week) > 227 ng/mL (50 mg 1 to 3 times/week). The impact on Cmin was variable in patients whose dose or therapeutic scheme was changed, especially when administered the intermittent infusion of amphotericin B. The mean Cmin for each LAmB schedule of intermittent therapy was equal or higher than the minimum inhibitory concentration of amphotericin B against Cryptococcus isolates from 10/12 patients. The Cmin of amphotericin B in patients with cryptococcal meningitis was comparable between those that survived or died. Conclusions: By evaluating the Cmin of amphotericin B, we demonstrated the therapeutic potential of its intermittent use including in the consolidation phase of neurocryptococcosis treatment, despite the great variability in serum levels among patients.

Neurocriptococose em paciente imunocompetente: um relato de caso

“…Essa associação de terapia antifúngica é bem estabelecida na literatura, com melhora da sobrevida nos pacientes que usam a flucitosina (DAY JN, et al, 2014). Todavia, não há disponibilidade no Brasil desta droga, sendo optada pela terapêutica de manutenção com fluconazol na paciente do caso descrito, além de maiores doses de anfotericina B objetivando atingir a dose cumulativa de 2000 a 3000 mg (SCHIAVE et al, 2020). O sucesso do tratamento com o fluconazol deve-se aos níveis séricos e no LCR adequados desta droga.…”

Case reports of invasive mucormycosis associated neutropenic enterocolitis in leukemic children: diagnostic and treatment challenges and review of literature

“…Although there is evidence that intermittent doses of L-AmB could prevent invasive fungal infections in immunocompromised hosts, some critical points should be considered. First, the effective prophylactic treatment with L-AmB is usually achieved by high-dose intermittent intravenous injections [ 34 – 36 ], so the similar effect may not be obtained by lower doses as recommended by current guidelines for prophylaxis treatment [ 37 , 38 ], which necessitates further investigation for determining optimal dosage and interval [ 39 ]. Second, the accumulation of the L-AmB varies according to the different body tissues during treatment [ 40 ].…”

Polyene Antibiotics Physical Chemistry and Their Effect on Lipid Membranes; Impacting Biological Processes and Medical Applications

“…Regardless of the dosage regimen, trough concentrations remained constant in patients, particularly those with cryptococcosis. It has therefore been suggested that intermittent administration regimens of liposomal AmB should be implemented in patients with mycoses [ 408 ].…”