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Antimicrobial Agents and Chemotherapy, September 2005, p. 3784-3788, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3784-3788.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Assessment of Effective Renal Plasma Flow, Enzymuria, and Cytokine Release in Healthy Volunteers Receiving a Single Dose of Amphotericin B Desoxycholate

Manjunath P. Pai,1* Jeffrey P. Norenberg,1 Robert A. Telepak,2 David S. Sidney,2 and Shu Yang2

College of Pharmacy,1 School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico2

Received 31 March 2005/ Returned for modification 4 June 2005/ Accepted 25 June 2005

The present study assessed potential subclinical markers of amphotericin B (AmB)-related nephrotoxicity and infusion-related reactions (IRR). Subjects were pretreated with diphenhydramine and acetaminophen and received a 500-ml bolus infusion of 0.9% sodium chloride prior to each effective renal plasma flow (ERPF) assessment. ERPF was measured before and after administration of a single 0.25-mg/kg intravenous AmB dose using technetium-99m mercaptoacetyltriglycine. Blood was collected before and 3 h after AmB infusion for tumor necrosis factor alpha (TNF-{alpha}) and interleukin-1ß (IL-1ß) plasma concentrations. Overnight 12-h urine collections were performed before administration of AmB and for 2 nights after administration of AmB and analyzed for {alpha} and {pi} glutathione-S-transferases (GST{alpha} and GST{pi}, respectively) and N-acetyl-ß-D-glucosaminidase (NAG). Six men and six women with mean ± standard deviation (SD) ages of 24.8 ± 5.3 and 28.0 ± 8.5 years, respectively, were studied. Baseline serum creatinine values were within the normal range and were unaltered after administration of AmB. The mean ± SD decrease in ERPF after administration of AmB was significant (P < 0.05) in males (15.7 ± 8.1%) but not females (9.5 ± 14.0%). The GST{pi} and GST{alpha} indices increased significantly (P < 0.05) by two to fourfold and returned to baseline in males but were unaltered in females. NAG indices were unaffected by AmB. Six patients experienced an IRR that was associated with increased TNF-{alpha} (P < 0.05) but not IL-1ß (P = 0.09). These results suggest a potential sex-related difference in AmB-induced nephrotoxicity and provide a rationale for use of ERPF, urine GST, and TNF-{alpha} as subclinical markers of polyene-induced toxicity.


* Corresponding author. Mailing address: College of Pharmacy, MSC09 5360, 1 University of New Mexico, Albuquerque, NM 87131-0001. Phone: (505) 272-8931. Fax: (505) 272-6749. E-mail: apai{at}salud.unm.edu.


Antimicrobial Agents and Chemotherapy, September 2005, p. 3784-3788, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3784-3788.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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