Influence of Drugs on Albumin and Bilirubin Interaction
作者:
Masahisa Funato,
Youkei Lee,
Shoju Onishi,
William J. Cashore,
期刊:
Pediatrics International
(WILEY Available online 1989)
卷期:
Volume 31,
issue 1
页码: 35-44
ISSN:1328-8067
年代: 1989
DOI:10.1111/j.1442-200X.1989.tb01267.x
出版商: Blackwell Publishing Ltd
数据来源: WILEY
摘要:
Twenty‐eight drugs, including cephem antibiotics and anti‐inflammatory agents currently used or considered potentially useful in neonatal intensive care nurseries in Japan, were examined to determine their influence on albumin and bilirubin interaction by means of a glucose oxidase ‐ peroxidase method, using an automated analyzer (Arrows) for unbound bilirubin (U.B.). The apparent binding constant for drugs to the high‐affinity site on albumin (KD) was determined. Of cephem. antibiotics, latamoxef sodium (LMOX) and cefazolin sodium (CEZ) were found to displace bilirubin from albumin (KD= 5.9 times 103M‐1and 4.5 times 103M‐1, respectively) as strongly as Na salicylate (KD= 6.8 times 103M‐1). Mephenamate and indomethacin, which are used for medical closure of patent ductus arteriosus in premature infants, were also found to be stronger bilirubin displacers (Kn = 1.3 times 105M‐1and 1.2 times 105M‐1, respectively) than sulfisoxazole (KD= 1.6 times 104M‐1). Maximal displacement factors (MDF's) were also estimated in reference to protein binding (%) and effective serum concentration (M) of each drug in human adults. Of these drugs, mephenamate showed a higher risk of bilirubin displacement (MDF = 3.79) than sulfisoxazole (MDF = 2.58) and LMOX had a higher risk of displacement (MDF = 1.97) than Na salicylate (MDF = 1.85). On the other hand, indomethacin and CEZ showed minimal effects on displacement at therapeutic levels (MDF = 1.03 and 1.00, respectively). At therapeutic serum levels, mephenamate and LMOX may possess the potential for displacing bilirubin from albumin and increasing the risk of bilirubin encephalopathy, in a manner simil
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