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 L-AmB 50 mg resulted in a similar Cmin, but a significant increase ocurred with L-AmB 100 mg/day. The geometric mean Cmin tended to decrease with a reduction in the dose and frequency of intermittent L-AmB 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 L-AmB 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.

Pattern of serum bile acids in patients with hepatic fascioliasis

The study included 20 patients with established Fasciola infection and 10 normal healthy control subjects. Total serum bile acids and the individual bile acids; cholic acid [CA], chenodeoxycholic acid [CDCA] and deoxycholic acid [DCA] were estimated using reversed phase high performance liquid chromatography. Total serum bile acids, CA levels and their percentage from the total were significantly increased in thefasciola group than in the controls. There was also a significant decrease in the percentage of DCA from the total bile acids as well as its ratio to CA. This decrease might be due to the absence of DCA in some fasciola patients [55%] and to the significant increase in CA which favours more a cholestatic lesion in such patients. All the results of liver function tests were within the accepted normal limits. It could be concluded that, in cases of fascioliasis in the absence of abnormalities in the usual liver function tests especially in anicteric subjects, evaluation of total serum bile acids, CA, DCA levels and the ratio DCA/CA should be considered to demonstrate any minor abnormalities in hepatobiliary system