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

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Published in	Antimicrobial Agents and Chemotherapy Vol. 49; no. 9; pp. 3784 - 3788
Main Authors	Pai, Manjunath P., Norenberg, Jeffrey P., Telepak, Robert A., Sidney, David S., Yang, Shu
Format	Journal Article
Language	English
Published	Washington, DC American Society for Microbiology 01.09.2005
Subjects	Adolescent Adult Aged Amphotericin B Amphotericin B - adverse effects Amphotericin B - pharmacology Antibiotics. Antiinfectious agents. Antiparasitic agents Antifungal Agents Antifungal Agents - adverse effects Antifungal Agents - pharmacology Biological and medical sciences Clinical Therapeutics Creatinine - blood Cytokines Cytokines - metabolism Deoxycholic Acid Deoxycholic Acid - adverse effects Deoxycholic Acid - pharmacology Drug Combinations Enzymes Enzymes - urine Female Humans Interleukin-1 - biosynthesis Kidney Function Tests Male Medical sciences Middle Aged Pharmacology. Drug treatments Renal Plasma Flow Renal Plasma Flow - drug effects Tumor Necrosis Factor-alpha - biosynthesis Human Evaluation Biological fluid Healthy subject Cytokine Single dose Kidney Blood plasma Antiprotozoal agent Antibiotic Antifungal agent Amphotericin B Polyenic compound Efficiency Parasiticide Release
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ISSN	0066-4804 1070-6283 1098-6596 1098-6596
DOI	10.1128/AAC.49.9.3784-3788.2005

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Abstract	A correction has been published Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology. For an alternate route to AAC .asm.org, visit: AAC
AbstractList	A correction has been published Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology. For an alternate route to AAC .asm.org, visit: AAC 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-1beta (IL-1beta) 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 (GSTalpha and GSTpi, respectively) and N-acetyl-beta-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 GSTpi and GSTalpha 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-1beta (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.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-1beta (IL-1beta) 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 (GSTalpha and GSTpi, respectively) and N-acetyl-beta-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 GSTpi and GSTalpha 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-1beta (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. 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-α) and interleukin-1β (IL-1β) plasma concentrations. Overnight 12-h urine collections were performed before administration of AmB and for 2 nights after administration of AmB and analyzed for α and π glutathione-S-transferases (GSTα and GSTπ, respectively) and N-acetyl-β-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 GSTπ and GSTα 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-α (P < 0.05) but not IL-1β (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-α as subclinical markers of polyene-induced toxicity. 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-1 beta (IL-1 beta ) 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- beta -D-glucosaminidase (NAG). Six men and six women with mean plus or minus standard deviation (SD) ages of 24.8 plus or minus 5.3 and 28.0 plus or minus 8.5 years, respectively, were studied. Baseline serum creatinine values were within the normal range and were unaltered after administration of AmB. The mean plus or minus SD decrease in ERPF after administration of AmB was significant (P < 0.05) in males (15.7 plus or minus 8.1%) but not females (9.5 plus or minus 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-1 beta (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. 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-1beta (IL-1beta) 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 (GSTalpha and GSTpi, respectively) and N-acetyl-beta-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 GSTpi and GSTalpha 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-1beta (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. 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-α) and interleukin-1β (IL-1β) plasma concentrations. Overnight 12-h urine collections were performed before administration of AmB and for 2 nights after administration of AmB and analyzed for α and π glutathione- S -transferases (GSTα and GSTπ, respectively) and N -acetyl-β- 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 GSTπ and GSTα 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-α ( P < 0.05) but not IL-1β ( 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-α as subclinical markers of polyene-induced toxicity.
Author	David S. Sidney Robert A. Telepak Jeffrey P. Norenberg Manjunath P. Pai Shu Yang
AuthorAffiliation	College of Pharmacy, 1 School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 2
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Keywords	Human Evaluation Biological fluid Healthy subject Cytokine Single dose Kidney Blood plasma Antiprotozoal agent Antibiotic Antifungal agent Amphotericin B Polyenic compound Efficiency Parasiticide Release
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Notes	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 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@salud.unm.edu.
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Snippet	A correction has been published Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg... The present study assessed potential subclinical markers of amphotericin B (AmB)-related nephrotoxicity and infusion-related reactions (IRR). Subjects were...
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SubjectTerms	Adolescent Adult Aged Amphotericin B Amphotericin B - adverse effects Amphotericin B - pharmacology Antibiotics. Antiinfectious agents. Antiparasitic agents Antifungal Agents Antifungal Agents - adverse effects Antifungal Agents - pharmacology Biological and medical sciences Clinical Therapeutics Creatinine - blood Cytokines Cytokines - metabolism Deoxycholic Acid Deoxycholic Acid - adverse effects Deoxycholic Acid - pharmacology Drug Combinations Enzymes Enzymes - urine Female Humans Interleukin-1 - biosynthesis Kidney Function Tests Male Medical sciences Middle Aged Pharmacology. Drug treatments Renal Plasma Flow Renal Plasma Flow - drug effects Tumor Necrosis Factor-alpha - biosynthesis
Title	Assessment of Effective Renal Plasma Flow, Enzymuria, and Cytokine Release in Healthy Volunteers Receiving a Single Dose of Amphotericin B Desoxycholate
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