The binding of sulfaphenazole to fetal, neonatal, and adult human plasma albumin

Chignell, Colin F.; Vesell, Elliot S.; Starkweather, Donnas K.; Berlin, Cheston M.

doi:10.1002/cpt1971126897

Cited by 58 publications

(18 citation statements)

References 2 publications

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“…In support of this, cord and adult albumin, isolated by a simple salting-out technique, were reported to differ in electrophoretic and chromatographic properties and to vary in resistance to alkali and proteolytic enzymes (5,6). However, authors of subsequent papers questioned the existence of a functionally immature albumin and attributed the reduced binding of newborn serum to competitive binding by increased concentrations of certain metabolites such as arachidonic acid and hematin (7)(8)(9)(10)(11).…”

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confidence: 99%

Fetal and adult albumins are indistinguishable by immunological and physicochemical criteria

Gitzelmann-Cumarasamy

Gitzelmann²,

Wilson

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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The existence of a functionally immature fetal albumin has been postulated to explain the reduced ability of newborn plasma to bind bilirubin and various drugs. In support of this, cord and adult albumin, isolated by a simple salting-out technique, were reported to differ in electrophoretic and chromatographic properties and in their resistance to alkali and proteolytic enzymes. However, the interpretation of these findings has since been questioned. To resolve this controversy, we have purified to homogeneity human serum albumins from pooled umbilical cord and adult donor plasma. The two albumins were compared and found to be indistinguishable by polyacrylamide gel electrophoresis with and without sodium dodecyl sulfate, as well as by immunoelectrophoresis and double immunodiffusion using specific antibodies against both albumins. Furthermore, the amino acid compositions, the aminoterminal sequence (Asp-Ala-His-Lys-Ser-Glu-Val-Ala-), the carboxy terminus (Leu), and the peptide fingerprints were identical in the two albumins. No significant differences were found by circular dichroism in the ultraviolet (200-350 nm). Binding studies with bilirubin showed association constants of 3.7 + 0.7 X 107 M-1 for cord and 2.9 : 0.3 X 107 M-' for adult albumin, respectively. The circular dichroic spectra of 1:1 bilirubin-albumin complexes showed considerable variation between the batches but were not significantly different. The only difference was found in the fluorescence spectra of the bilirubin-albumin complexes, in which complexes with adult albumin showed only 75% of the relative fluorescence exhibited with cord albumin. The combined results nevertheless strongly indicate that fetal and adult albumins are very similar, if not identical. Human serum albumin is an almost universal carrier for a host of metabolites and drugs (1). As such it plays a central role in the regulation of their activity or toxicity. This is of particular significance in neonatal medicine because newborns, with their immature detoxifying mechanisms (for review see ref.2), are highly susceptible to various toxic agents. A well-known example is bilirubin encephalopathy resulting from neonatal jaundice.During clinical studies it was observed that newborn serum has a lower ability to bind bilirubin and drugs than adult serum does (refs. 3 and 4 and references cited therein). To explain these observations, the existence of a fetal type of albumin, analogous to hemoglobin F, was postulated. In support of this, cord and adult albumin, isolated by a simple salting-out technique, were reported to differ in electrophoretic and chromatographic properties and to vary in resistance to alkali and proteolytic enzymes (5, 6). However, authors of subsequent papers questioned the existence of a functionally immature albumin and attributed the reduced binding of newborn serum to competitive binding by increased concentrations of certain metabolites such as arachidonic acid and hematin (7-11).To resolve this controversy, we purified cord and adult albumin...

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mentioning

confidence: 99%

Fetal and adult albumins are indistinguishable by immunological and physicochemical criteria

Gitzelmann-Cumarasamy

Gitzelmann²,

Wilson

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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“…Since antimicrobial agents are frequently administered to such patients, an eluci dation of the interaction between antimicrobials and bilirubin is of potential clinical importance. Previous reports have shown that the binding of sulfaphenazole to albumin may be influenced by bilirubin (7). The present study is focused on how the protein binding of several antimicrobial agents in vitro is affected by unconjugated bilirubin.…”

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confidence: 99%

Displacement of Albumin-Bound Antimicrobial Agents by Bilirubin

Bratlid¹,

Bergan²

1976

Pharmacology

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The ability of bilirubin to displace antimicrobial agents from their binding sites on albumin was studied in vitro by equilibrium dialysis. Sulfonamides, tetracyclines, penicillins and cephalosporins of different degrees of protein binding were tested. It was found that bilirubin reduced the protein binding of all four classes of antimicrobial agents, although by varying degrees. This effect was most pronounced with the compounds which had the highest degree of protein binding, such as cloxacillin, cephazolin, methacycline and sulfisoxazole, all of which are bound greater than 80 % by albumin. On the other hand, the drugs with less than 25 % binding, such as ampicillin, cephalexine and tetracycline were not ostensibly displaced by bilirubin. Scatchard plots of the binding of sulfamethoxazole to albumin in the presence of 400 μmol/l of bilirubin, showed that bilirubin almost completely displaced the sulfonamide molecule from the high affinity site on the albumin molecule. Reduced protein binding of drugs in hyperbilirubinemic infants may have pharmacokinetic significance.

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“…Several recent studies have indicated that numerous drugs are bound less extensively to plasma proteins of the newborn human infant than in plasma of the adult [2,6,8,12]. This phenomena has generally been attributed to lower albumin levels of the infant at birth and to competition for binding sites by endogenous ligands such as bilirubin, sex hormones and fatty acids.…”

Section: Introductionmentioning

confidence: 99%

Binding of <sup>14</sup>C-Salicylic Acid and <sup>14</sup>C-PentobarbitaI to Plasma Proteins of Several Species During the Perinatal Period

Ce¹,

Sexton²,

McFarland³

1975

Neonatology

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The fractional binding of ¹⁴C-salicylic acid and ¹⁴C-pentobarbital was studied as a function of age in plasma of the pig, dog, goat and human. The pig exhibited an unusual degree of hypoalbuminemia and low fractional binding of salicylic acid at birth. Albumin levels and the percent binding of salicylic acid were not significantly lower in newborn plasma than in adult plasma of the other species studied. The pig was also exceptional in that the high fractional binding of pentobarbital observed at low Iigand concentrations in plasma of the newborn was not observed in the other species studied. Depletion of albumin in newborn pig plasma did not appreciably affect the binding of pentobarbital. Thus it is suggested that the plasma of the fetal and newborn pig may contain a nonalbuminoid protein, such as a fetal globulin, which is capable of binding pentobarbital but does not have a high avidity for salicylic acid. It apparently does not exist at birth in the plasmas of the other species studied, as depletion of albumin markedly reduced the fractional binding of pentobarbital.

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The binding of sulfaphenazole to fetal, neonatal, and adult human plasma albumin

Cited by 58 publications

References 2 publications

Fetal and adult albumins are indistinguishable by immunological and physicochemical criteria

Fetal and adult albumins are indistinguishable by immunological and physicochemical criteria

Displacement of Albumin-Bound Antimicrobial Agents by Bilirubin

Binding of <sup>14</sup>C-Salicylic Acid and <sup>14</sup>C-PentobarbitaI to Plasma Proteins of Several Species During the Perinatal Period

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