Investigations on salicylate protein binding in newborns and infants

Windorfer, A; Karitzky, D; Gasteiger, U.; Stehr, K.

doi:10.1007/bf00442057

Cited by 11 publications

(6 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 86%

See 1 more Smart Citation

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

Viani

Cappiello²,

Pacifici³

1991

Dev Pharmacol Ther

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 86%

“…This finding may be due, at least in part, to the greater concentration of bilirubin bound to fetal albumin, bilirubin being a powerful displacer of salicylic acid [6].…”

Section: Discussionmentioning

confidence: 99%

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

Viani

Cappiello²,

Pacifici³

1991

Dev Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…Most drugs taken by the nursing mother will be partially excreted into her milk and ingested by the suckling infant [1,11,16]. On the other hand, digoxin is given in rather high dosage (related to body weight) in cardiac failure of newborns and infants and though the half-life is equal or even shorter nential functions.…”

Section: Discussionmentioning

confidence: 99%

“…At this time the suckling infant inevitably participates in medications applied to the mother [1,11,16].…”

Section: Introductionmentioning

confidence: 99%

Kinetics of the translactal passage of digoxin from breast feeding mothers to their infants

et al. 1982

View full text Add to dashboard Cite

In order to find out whether digoxin therapy of nursing mothers might produce discomfort in suckling infants we have investigated the kinetics of the transfer of digoxin from plasma to milk in 11 nursing mothers. After intravenous or oral application of a single dose of 0.5 mg or 0.75 mg digoxin simultaneous serum, fore- and hindmilk samples were taken. Obviously, a rapid equilibrium occurred between the serum and the milk compartments and there was no difference between fore- and hindmilk. All three digoxin concentration profiles ran parallel with a milk to serum ratio of 0.6 to 0.7. The curves could best be fitted by the sum of two exponential functions. For predicting the digoxin intake into the suckling infant, simulations were carried out on the basis of two coupled compartment models. When the kinetic milk data as well as the kinetic data obtained in infants were fitted by this model it could be shown that even in the case of long half-lives only about 3% of the therapeutic drug levels were reached in the baby. Thus, one can conclude that digoxin accumulation to toxic concentrations should not occur in infants of women treated with appropriate doses of digoxin.

show abstract

“…This has been taken into account in risk assessment of sub chronic studies. The distribution of the substance may be different from that in adults due to, for instance, differences in body composition, regional blood flow, organ perfusion and cardiac output and plasma protein-binding capacity between infants and adults (Fredholm et al, 1975;Windorfer et al, 1978;Friis-Hansen, 1983;Mielke and Gundert-Remy, 2009). The capacity of enzymes involved in phases I and II metabolism is generally up to two-(full term) to threefold (preterm) lower when comparing infants with healthy adults.…”

mentioning

confidence: 99%

Scientific opinion on pesticides in foods for infants and young children

Ockleford¹,

Adriaanse²,

Bennekou³

et al. 2018

EFS2

View full text Add to dashboard Cite

Following a request from the European Commission, the EFSA Panel on Plant Protection Products and their Residues (PPR Panel) prepared a scientific opinion to provide a comprehensive evaluation of pesticide residues in foods for infants and young children. In its approach to develop this scientific opinion, the EFSA PPR Panel took into account, among the others, (i) the relevant opinions of the Scientific Committee for Food setting a default maximum residue level (MRL) of 0.01 mg/kg for pesticide residues in foods for infants and young children; (ii) the recommendations provided by EFSA Scientific Committee in a guidance on risk assessment of substances present in food intended for infants below 16 weeks of age; (iii) the knowledge on organ/system development in infants and young children. For infants below 16 weeks of age, the EFSA PPR Panel concluded that pesticide residues at the default MRL of 0.01 mg/kg for food for infants and young children are not likely to result in an unacceptable exposure for active substances for which a health-based guidance value (HBGV) of 0.0026 mg/kg body weight (bw) per day or higher applies. Lower MRLs are recommended for active substances with HBGVs below this value. For infants above 16 weeks of age and young children, the established approach for setting HBGVs is considered appropriate. For infants below 16 weeks of age the approach may not be appropriate and the application of the EFSA guidance on risk assessment of substances present in food intended for infants below 16 weeks of age is recommended. The contribution of conventional food to the total exposure to pesticide residues is much higher than that from foods intended for infants and young children. Because of the increased intake of conventional food by young children, these have the highest exposure to pesticide residues, whereas infants 3-6 months of age generally have lower exposure. The impact of cumulative exposure to pesticide residues on infants and young children is not different from the general population and the EFSA cumulative risk assessment methodology is also applicable to these age groups. Residue definitions established under Regulation (EC) No 396/2005 are in general considered appropriate also for foods for infants and young children. However, based on a tier 1 analysis of the hydrolysis potential of pesticides simulating processing, the particular appropriateness of existing residue definitions for monitoring to cover processed food, both intended for infants and young children as well as conventional food, is questionable.

show abstract

Investigations on salicylate protein binding in newborns and infants

Cited by 11 publications

References 29 publications

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

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

Kinetics of the translactal passage of digoxin from breast feeding mothers to their infants

Scientific opinion on pesticides in foods for infants and young children

Contact Info

Product

Resources

About