scholarly journals Dose-Dependent Pharmacokinetics of Amphotericin B Lipid Complex in Rabbits

2000 ◽  
Vol 44 (8) ◽  
pp. 2068-2076 ◽  
Author(s):  
Thomas J. Walsh ◽  
Andre J. Jackson ◽  
James W. Lee ◽  
Michael Amantea ◽  
Tin Sein ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Fungal Infections ◽  
Rabbit Model ◽  
Time Dependent ◽  
Antifungal Compound ◽  
Lipid Complex ◽  
Detailed Model ◽  
Amphotericin B Lipid Complex ◽  
Cellular Components

ABSTRACT Amphotericin B lipid complex (ABLC) was recently approved by the Food and Drug Administration for treatment of patients with invasive fungal infections who are intolerant of or refractory to conventional amphotericin B therapy. Little is known, however, about the pharmacokinetics of this new antifungal compound. We therefore investigated the pharmacokinetics of ABLC in comparison with those of conventional desoxycholate amphotericin B (DAmB) in rabbits. The pharmacokinetics of DAmB in a rabbit model were similar to those previously reported in humans. The pharmacokinetics of ABLC differed substantially from those of DAmB. Plasma amphotericin B levels following ABLC administration were 10 times lower than those following administration of an equal dosage of DAmB. The levels of ABLC in whole blood were approximately 40 times greater than those in plasma. The ABLC model differed from the DAmB model by (i) a dose- and time-dependent uptake and return between the plasma compartment and apparent cellular components of the blood-sediment compartment and (ii) time-dependent tissue uptake and return to plasma from serially connected compartments. Following infusion of ABLC, there was a nonlinear uptake into the apparent cellular components of the blood-sediment compartment. This uptake was related to the reciprocal of the integral of the total amount of drug infused (i.e., the more drug infused the greater the fractional uptake between 0.5 and 5 mg/kg of body weight for ABLC). The transfer of drug from plasma to the cellular components of the blood-sediment compartment resulted in initial uptake followed by rapid redistribution back to the plasma. The study describes a detailed model of the pharmacokinetics of ABLC and characterizes a potential role of the cellular components of the blood-sediment compartment in the distribution of this new antifungal compound in tissue.

Two-year Longitudinal Evaluation of Amphotericin B Lipid Complex Injection in a Tertiary Care Medical Center

2000 ◽  
Vol 35 (2) ◽  
pp. 176-181 ◽  
Author(s):  
Leanne D. Kennedy ◽  
Julie F. Connelly ◽  
Kevin M. Kuzma
Keyword(s):  
Serum Creatinine ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Tertiary Care ◽  
Serum Creatinine Concentration ◽  
Creatinine Concentration ◽  
Lipid Complex ◽  
Tertiary Care Medical Center ◽  
Amphotericin B Lipid Complex ◽  
The Mean

A 2-year concurrent drug use evaluation was conducted in 156 patients to determine whether Abelcet (amphotericin B lipid complex injection) was being prescribed according to institution-approved guidelines and to characterize the patient population receiving Abelcet. Eighty-nine patients (57%) had fungal infections documented by chest x-ray, computed tomography, or fungal cultures. Sixty-seven (43%) had clinically suspected fungal infections. The Abelcet mean dose by weight was 5 mg/kg/day (actual body weight). Seventy-one patients (46%) met the established guidelines for use; 85 (54%) did not. Premedication was given to 64% of the patients; only 15 patients (10%) experienced documented fever and chills. A total of 72 patients (46%) died during therapy. Of the 75 patients who completed therapy in the hospital, 41 were switched to conventional amphotericin B, fluconazole, or itraconazole following a decrease in serum creatinine concentration, and 34 did not receive further antifungal therapy. The mean length of Abelcet therapy was 11 days. The mean increase in serum creatinine concentration at discontinuation of therapy was 0.2 mg/dL. Continued monitoring of Abelcet use was recommended and established guidelines were reaffirmed. Hydration with normal saline before and after dosing was suggested to help improve renal function, and dopamine was recommended to increase renal blood flow.

scholarly journals Amphotericin B Lipid Complex for Invasive Fungal Infections: Analysis of Safety and Efficacy in 556 Cases

1998 ◽  
Vol 26 (6) ◽  
pp. 1383-1396 ◽  
Author(s):  
Thomas J. Walsh ◽  
John W. Hiemenz ◽  
Nita L. Seibel ◽  
John R. Perfect ◽  
Gary Horwith ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Lipid Complex ◽  
Safety And Efficacy ◽  
Amphotericin B Lipid Complex

Antifungal Prophilaxis with Low Dose Amphotericin B Lipid Complex In Patients with Acute Myeloid Leukaemia: A Single Centre Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4303-4303
Author(s):  
Barbara Veggia ◽  
Francesca Saltarelli ◽  
Enrico Montefusco ◽  
Esmeralda Conte ◽  
Giusy Antolino ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Low Dose ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Cell Transplant ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Lipid Complex ◽  
Amphotericin B Lipid Complex ◽  
Acute Myeloid

Abstract Abstract 4303 INTRODUCTION Invasive fungal infections (IFI) represent an important cause of mortality and morbidity in patients with Acute Myeloid Leukemia (AML) undergoing intensive chemotherapy. A prophylactic antifungal therapy is often administered during intensive chemotherapy, however the optimal antifungal prophylaxis protocol is still unknown. Amphotericin B lipid complex (Abelcet®) has been commonly used as a standard treatment for IFIs caused by Aspergillus and Candida, but its effectiveness in prophilaxis has not been clearly estabilished. METHODS From September 2010 to April 2011 we treated six patients with newly diagnosed AML using low dose amphotericin B lipid complex as antifungal prophilaxis. Patients observed were three females and 3 males, median age was 54 years (range 21–74 years) and they were all fit to receive intensive chemotherapy. Three patients older than 60 years received Fludarabine based chemotherapy regimen during both induction and consolidation. Three patients aged less than 60 years old were treated using a chemotherapy protocol based on Citarabine, Daunorubicin and Ethoposide association. One patient in this group also underwent BuCy conditioned autologous stem cell transplant. Amphotericin B lipid complex was administered intravenously at 100 mg once a day. Antifungal prophilaxis was started when the absolute neutrophil count was ≤ 500 cells/μ l and was continued until neutrophils recovery was ≥ 500 cells/μ l, without any evidence of IFI. RESULTS Five patients did not experience any proven fungal infection during all treatment. Anyway one patient died during induction due to a severe bacterial lung infection. One patients discontinued antifungal prophylaxis due to extensive skin rash during the second infusion of the drug. Amphotericin B lipid complex was otherwise well tolerated by patients. One patient was diagnosed with lung aspergillosis infection by evidence of galattomannan positivity on BAL and a lung CT scan showing a single nodular escavated lesion on left upper lobe; subsequentely he was successfully treated with voriconazole. CONCLUSIONS In our experience, Amphotericin B lipid complex showed to be an effective and safe antifungal prophylaxis for newly diagnosed AML patients. Further clinical studies are certainly required to obtain definitive data. Disclosures: No relevant conflicts of interest to declare.

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