Binding of furosemide to albumin isolated from adult and fetal human serum

Viani, A; Cappiello, Mario; Pacifici, Gian Maria

doi:10.1016/1043-6618(90)90795-f

Cited by 4 publications

(9 citation statements)

References 1 publication

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“…Fetal and adult albumin thus have similar binding properties for diazepam, salicylic acid and digitoxin, and these results corrobo rate our previous findings with furosemide [12], The lower binding of diazepam [7] and salicylic acid [6] in fetal than in adult serum may not be due to lower intrinsic binding properties of fetal albumin.…”

Section: Discussionsupporting

confidence: 79%

“…After extensive dialysis of serum, the unbound fraction of furosemide becomes similar in fetal and adult sera [3], The defect of binding in fetal serum may thus be due to dialyzable endogenous compounds. This hypothesis was corroborated by using isolated fetal and adult human albumin, the binding of furose mide being similar in the two albumin prep arations [12].…”

Section: Introductionsupporting

confidence: 59%

“…It was interesting to ascertain whether diazepam and digitoxin bind to fe tal and adult albumin similarly. It was also interesting to verify whether our previous findings with furosemide [12] apply to sali cylic acid, these drugs binding to the same site of albumin.…”

Section: Introductionmentioning

confidence: 99%

“…Human adult plasma (total volume about 1 liter), obtained from the blood bank of the University Hospital of Pisa, was stored at -80 °C for a week. Albumin was isolated from fetal and adult plasma as described by Curling et al [15], and the entire procedure for fetal and adult albumin has been previously described [12]. The con centrations of endogenous biliburin and nonesterified fatty acids bound to albumin were 0.3 mg/g albumin and 9.1 mEq/g albumin, respectively (fetal albumin), and 0.06 mg/g adult albumin and 9.8 mEq/g albumin, respectively (adult albumin).…”

Section: Biological Materialsmentioning

confidence: 99%

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Binding of Diazepam, Salicylic Acid and Digitoxin to Albumin Isolated from Fetal and Adult Serum

Viani

Cappiello²,

Pacifici³

1991

Dev Pharmacol Ther

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Albumin was isolated from pooled fetal serum obtained at normal delivery at term and from pooled adult plasma. Albumin isolation was carried out by means of PEG precipitation followed by ion exchange chromatography on DEAE-Sephadex A 50 and then on SP-Sephadex C 50. The binding of diazepam (1 μM), salicylic acid (2 mM) and digitoxin (6 nM) to albumin (40 g/l) was measured by equilibrium dialysis at 37°C. The unbound fraction (mean ± SD) for fetal and adult albumin of diazepam was 1.86 ± 0.24 and 1.82 ± 0.15% (NS), that of digitoxin was 3.18 ± 0.27 and 3.36 ± 0.04% (NS) and that of salicylic acid was 11.65 ± 0.99 and 9.47 ± 0.75% (p < 0.05), respectively. With both fetal and adult albumin, a single class of binding sites was observed for diazepam and digitoxin, whereas two classes of binding sites were observed for salicylic acid. The number of binding sites (n, moles of drug per mole of albumin) for fetal and adult albumin was 0.83 and 1.02 for diazepam and 0.014 and 0.018 for digitoxin, respectively. For salicylic acid, n was 1.45 (fetal albumin) and 1.55 (adult albumin) for the higher affinity site, and 3.06 (fetal albumin) and 3.27 (adult albumin) for the lower affinity site. The association constant (K(a), M^-1) for diazepam was 1.36 × 10^5 (fetal albumin) and 1.00 × 10^5 (adult albumin) and that for digitoxin was 4.12 × 10^6 (fetal albumin) and 2.7 × 10^6 (adult albumin). For salicylic acid, K(a) was 38.4 × 10^3 (fetal albumin) and 35.8 × 10^3 (adult albumin) for the higher affinity site, and 2.7 × 10^3 (fetal albumin) and 4.3 × 10^3 (adult albumin) for the lower affinity site. This work shows that fetal and adult albumin have similar binding properties and corroborates our previous findings with furosemide.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Section: Biological Materialsmentioning

confidence: 99%

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Binding of Diazepam, Salicylic Acid and Digitoxin to Albumin Isolated from Fetal and Adult Serum

Viani

Cappiello²,

Pacifici³

1991

Dev Pharmacol Ther

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“…Furosemide [9] and diazepam, salicylic acid and digitoxin [10] bind to a similar extent to equimolar solutions of newborn and adult albumin, thus suggesting that newborn and adult albumin have similar intrinsic binding properties. The role of hypoalbuminemia in the decreased binding of furosemide in newborn plasma was unknown.…”

Section: Introductionmentioning

confidence: 90%

Quantitative Contribution of Endogenous Compounds and Hypoalbuminemia in Reducing the Binding of Furosemide in the Plasma of Newborn Infants

Viani

Pacifici²

1992

Dev Pharmacol Ther

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The protein binding of furosemide was studied in the plasma of newborn infants and adult subjects. Plasma consisted of two pools obtained from 25 newborns and adult subjects. The concentrations of albumin were 36.8 (newborn) and 48.3 g/l (adult). The unbound fraction of furosemide was 1.38 ± 0.15 (adult) and 2.03 ± 0.13 % (newborn; p < 0.001). After extensive dialysis of the plasma, the unbound fraction of furosemide was 1.12 ± 0.15 (adult) and 1.39 ± 0.09% (newborn; p < 0.0001), suggesting that dialyzable endogenous compounds interfere with the binding of furosemide. The addition of human albumin to the newborn plasma to give a final albumin concentration of 48.3 g/l yielded an unbound fraction of furosemide of 1.63 ± 0.08 (nondialyzed plasma) and 1.17 ± 0.08% (dialyzed plasma; p < 0.0001). The addition of albumin to the dialyzed newborn plasma, to give a final albumin concentration similar to that in adult plasma, decreased the unbound furosemide to the level of the dialyzed adult plasma. The binding defect of furosemide in newborn plasma reflects either the effects of the endogenous inhibitors or of hypoalbuminemia. The intrinsic binding properties for furosemide of newborn dialyzed plasma are similar to those of dialyzed adult plasma. This consideration corroborates our previous results on the binding of furosemide and diazepam, salicylic acid and digitoxin to newborn and adult albumin. The displacement of furosemide by salicylic acid, tolbutamide and azapropazone is 70% greater in newborn than in adult plasma. The greater displacing effect is largely due to hypoalbuminemia.

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