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Article: Pharmacokinetics and adverse effects of amphotericin B in infants and children

TitlePharmacokinetics and adverse effects of amphotericin B in infants and children
Authors
Issue Date1988
PublisherMosby, Inc. The Journal's web site is located at http://www.elsevier.com/locate/jpeds
Citation
Journal Of Pediatrics, 1988, v. 113 n. 3, p. 559-563 How to Cite?
AbstractThe pharmacokinetics and safety of amphotericin B infusion were studied in 13 infants and children (age range 3 weeks to 18 years; median age 11 years) treated with the drug proved (n = 11) or suspected (n = 2) fungal infections. The dose during the first day was 0.5 mg/kg, followed by a daily dose of 1 mg/kg for the rest of the treatment period in most patients. The drug was infused over 4 to 6 hours. During the first day, serum concentrations were above the target therapeutic level of 0.3 μg/ml in all patients at 2 and 6 hours from the start of the infusion, in 12 of 13 patients at 12 hours, but in only 6 of 13 patients at 24 hours. On the third day, all concentrations were >0.3 μg/ml throughout the 24-hour period, and in 12 of 13 patients were >0.5 μg/ml. The same kinetic profile prevailed on days 7 to 10 of therapy, with a tendency for increasing concentrations. Elimination half-life was 9.93 ± 1.5 hours (mean ± SEM), clearance rate 26 ± 5 ml/kg·hr, and distribution volume 378 ± 25 ml/kg. The half-life inversely correlated with patients' age. Pharmacokinetic values calculated during the first day were not different from those calculated on day 3. Significant decreases in hemoglobin, platelets, and serum potassium concentration were recorded along with significant increases in serum creatinine, urea, and aspartate transaminase values. Because of the large pharmacokinetic variability and the high rate of serious adverse effects, individualized dosing of amphotericin B based on therapeutic drug monitoring should be considered.
Persistent Identifierhttp://hdl.handle.net/10722/170228
ISSN
2015 Impact Factor: 3.89
2015 SCImago Journal Rankings: 1.849
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKoren, Gen_US
dc.contributor.authorLau, Aen_US
dc.contributor.authorKlein, Jen_US
dc.contributor.authorGolas, Cen_US
dc.contributor.authorBologaCampeanu, Men_US
dc.contributor.authorSoldin, Sen_US
dc.contributor.authorMacleod, SMen_US
dc.contributor.authorProber, Cen_US
dc.date.accessioned2012-10-30T06:06:50Z-
dc.date.available2012-10-30T06:06:50Z-
dc.date.issued1988en_US
dc.identifier.citationJournal Of Pediatrics, 1988, v. 113 n. 3, p. 559-563en_US
dc.identifier.issn0022-3476en_US
dc.identifier.urihttp://hdl.handle.net/10722/170228-
dc.description.abstractThe pharmacokinetics and safety of amphotericin B infusion were studied in 13 infants and children (age range 3 weeks to 18 years; median age 11 years) treated with the drug proved (n = 11) or suspected (n = 2) fungal infections. The dose during the first day was 0.5 mg/kg, followed by a daily dose of 1 mg/kg for the rest of the treatment period in most patients. The drug was infused over 4 to 6 hours. During the first day, serum concentrations were above the target therapeutic level of 0.3 μg/ml in all patients at 2 and 6 hours from the start of the infusion, in 12 of 13 patients at 12 hours, but in only 6 of 13 patients at 24 hours. On the third day, all concentrations were >0.3 μg/ml throughout the 24-hour period, and in 12 of 13 patients were >0.5 μg/ml. The same kinetic profile prevailed on days 7 to 10 of therapy, with a tendency for increasing concentrations. Elimination half-life was 9.93 ± 1.5 hours (mean ± SEM), clearance rate 26 ± 5 ml/kg·hr, and distribution volume 378 ± 25 ml/kg. The half-life inversely correlated with patients' age. Pharmacokinetic values calculated during the first day were not different from those calculated on day 3. Significant decreases in hemoglobin, platelets, and serum potassium concentration were recorded along with significant increases in serum creatinine, urea, and aspartate transaminase values. Because of the large pharmacokinetic variability and the high rate of serious adverse effects, individualized dosing of amphotericin B based on therapeutic drug monitoring should be considered.en_US
dc.languageengen_US
dc.publisherMosby, Inc. The Journal's web site is located at http://www.elsevier.com/locate/jpedsen_US
dc.relation.ispartofJournal of Pediatricsen_US
dc.subject.meshAdolescenten_US
dc.subject.meshAmphotericin B - Adverse Effects - Blood - Pharmacokineticsen_US
dc.subject.meshChilden_US
dc.subject.meshChild, Preschoolen_US
dc.subject.meshChromatography, High Pressure Liquiden_US
dc.subject.meshHumansen_US
dc.subject.meshInfanten_US
dc.subject.meshInfusions, Intravenousen_US
dc.subject.meshMycoses - Drug Therapyen_US
dc.titlePharmacokinetics and adverse effects of amphotericin B in infants and childrenen_US
dc.typeArticleen_US
dc.identifier.emailLau, A:asylau@hku.hken_US
dc.identifier.authorityLau, A=rp00474en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/S0022-3476(88)80653-X-
dc.identifier.pmid3411404-
dc.identifier.scopuseid_2-s2.0-0023758388en_US
dc.identifier.volume113en_US
dc.identifier.issue3en_US
dc.identifier.spage559en_US
dc.identifier.epage563en_US
dc.identifier.isiWOS:A1988Q018900029-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridKoren, G=36042259400en_US
dc.identifier.scopusauthoridLau, A=7202626202en_US
dc.identifier.scopusauthoridKlein, J=7404605257en_US
dc.identifier.scopusauthoridGolas, C=6603467299en_US
dc.identifier.scopusauthoridBologaCampeanu, M=6506857320en_US
dc.identifier.scopusauthoridSoldin, S=7102502534en_US
dc.identifier.scopusauthoridMacLeod, SM=23473764000en_US
dc.identifier.scopusauthoridProber, C=35944487000en_US

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