Effects of two antibiotics on hepatic function in low birth weight infants: ampicillin vs. cefotaxime.
In 21 low birth weight infants with two regimens of antibiotic therapy during the first 3 days of life possible hepatotoxic side effects were studied 8 days after the last administration of the tested drugs. Fourteen of the infants were treated with ampicillin/gentamicin and 7 received cefotaxime/gentamicin. The serum concentrations of total bile acids, the activities of transaminases in serum and the cumulative 15N excretion in urine after administration of 3 mg of 15N-labeled methacetin/kg of body weight were used as markers of hepatotoxic side effects. Neither the concentrations of total bile acids (22.6 +/- 12.1 and 19.4 +/- 10.8 mM, respectively) nor the activities of transaminases (alanine aminotransferase, 0.27 +/- 0.06 vs. 0.30 +/- 0.09 mumol/second/liter; aspartate aminotransferase, 0.46 +/- 0.11 vs. 0.49 +/- 0.10 mumol/second/liter) were different between the two groups. In contrast the cumulative 15N excretion in urine was significantly lower in the group treated with cefotaxime/gentamicin than in the group treated with ampicillin/gentamicin (17.2 +/- 6.4 vs. 33.0 +/- 5.1% of intake; P less than 0.01) and also lower than the reported age-related reference values. On the 28th day of life no differences could be found between the cumulative 15N excretion in the urine of the infants treated with cefotaxime/gentamicin and the reported age-related reference values of this test. The results indicate a limited capacity of the monooxygenase system of the liver of low birth weight infants during the first weeks of life and a specific reversible influence of cefotaxime on this hepatocellular system. Further investigations are required to evaluate the clinical relevance of this drug-specific inhibition of the hepatic monooxygenase pathway.
Boehm
G
G
Department of Pediatrics, University of Leipzig, Germany.
Senger
H
H
Spencker
F B
FB
Handrick
W
W
Teichmann
B
B
Krumbiegel
P
P
D000081:Acetamides; D000667:Ampicillin / Q000008:administration & dosage / Q000009:adverse effects*; D001647:Bile Acids and Salts / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002439:Cefotaxime / Q000008:administration & dosage / Q000009:adverse effects*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009584:Nitrogen / Q000652:urine; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D000637:Transaminases / Q000097:blood
D000081:Acetamides; D001647:Bile Acids and Salts; D005839:Gentamicins; C035495:methacetin; D000667:Ampicillin; D000637:Transaminases; D002439:Cefotaxime; D009584:Nitrogen; D001663:Bilirubin