Effects of Development, Aging, and Renal and Hepatic Insufficiency as well as Hemodialysis on the Plasma Concentrations of Albumin and α1-Acid Glycoprotein

Pacifici, Gian Maria; Viani, A; Taddeucci-Brunelli, G; Rizzo, G; Carrai, Maura; Schulz, Hans–Ulrich

doi:10.1097/00007691-198609000-00003

Cited by 66 publications

(30 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hypoalbuminaemia and hyperbilirubinaemia may be two important factors, non-esterified fatty acids being little affected by liver disease (Pacifici et al, 1986 centrifuged at 2000 g for 20 min in a refrigerated centrifuge and the plasma was stored at -80°C for 1-3 months.…”

Section: Introduction Methodsmentioning

confidence: 99%

Plasma protein binding of frusemide in liver disease: effect of hypoalbuminaemia and hyperbilirubinaemia.

Viani¹,

Carrai²,

Pacifici³

1989

Brit J Clinical Pharma

View full text Add to dashboard Cite

The binding of frusemide was studied in the plasma of 20 healthy subjects and 45 patients with liver disease. The unbound percentage (mean +/‐ s.d.) of frusemide was 1.64 +/‐ 0.21 healthy subjects) and 2.24 +/‐ 0.79 (patients) (P less than 0.01). By grouping the patients on the basis of plasma albuminaemia and bilirubinaemia four clusters namely: 'normal concentrations of albumin and bilirubin' (A), 'hyperbilirubinaemia and normal albumin concentration' (B), 'hypoalbuminaemia and normal bilirubin concentration' (C) and 'hypoalbuminaemia and hyperbilirubinaemia' (D) were defined. The unbound percentage of frusemide was 1.80 +/‐ 0.36 in (A); 2.44 +/‐ 1.05 in (B); 2.23 +/‐ 0.38 in (C); 2.76 +/‐ 0.77 in (D). The figure for healthy volunteers was not different from A, whereas it was significantly lower than those for B and D (P less than 0.01) and for C (P less than 0.05). A lowered binding of frusemide was associated with hypoalbuminaemia or hyperbilirubinaemia.

show abstract

Section: Introduction Methodsmentioning

confidence: 99%

Plasma protein binding of frusemide in liver disease: effect of hypoalbuminaemia and hyperbilirubinaemia.

Viani¹,

Carrai²,

Pacifici³

1989

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…The profiles for infants undergoing VPA monotherapy and combination therapy are indicated as solid and dashed lines, respectively. 20,21) In addition, albumin concentrations largely vary among infants since the rates of physical development markedly differ among them. 22) These factors may be mainly responsible for the fact that the unbound VPA concentrations in infants are wide-ranging, and that, generally, the measured value is much higher than the predicted value using the totalto-unbound relationship profile of VPA provided for older children (Fig.…”

Section: Fig 2 Simulated Relationship Profiles Between the Total Anmentioning

confidence: 99%

“…Such a property of the parameter Kd was also observed in various studies previously reported, 10,25) and these results can be interpreted to reflect the fact that the serum albumin concentration in infants increases according to their physical development, while the protein-binding affinity of VPA is little affected by the physical development. 20,21) However, an additional investigation may be necessary to clearly explain that the protein-binding affinity in infants is not affected by the physical development, since it has been reported for various compounds that the protein-binding affinity to albumin decreases in infants, due to increased plasma concentrations of endogenous substances, including bilirubin and fatty acids. 21,26,27) It was also indicated that the binding ability of the serum albumin with various drugs is reduced in infants, due to the persistence of a functionally immature serum albumin.…”

Section: Fig 2 Simulated Relationship Profiles Between the Total Anmentioning

confidence: 99%

Empirical Approach for Improved Estimation of Unbound Serum Concentrations of Valproic Acid in Epileptic Infants by Considering Their Physical Development

Ueshima

Aiba

Sato

et al. 2011

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Valproic acid (VPA) is known to have a broad antiepileptic spectrum for partial and generalized seizures, and it has also been shown to be effective for intractable epilepsy when used at a higher dose than that generally recommended.1,2) With these properties, it is one of the widely prescribed compounds for epilepsy, but it should be noted that an excess increase in the serum VPA concentration inevitably elevates the risk of adverse reactions, such as hepatic dysfunction, 3) thrombocytopenia, 4) and hyperammonemic encephalopathy. 5)Since it has been considered that the unbound serum VPA concentration is closely related to the antiepileptic action of VPA and its adverse effects, 6) determination of the unbound VPA concentration via therapeutic drug monitoring (TDM) is essential to optimize the therapeutic efficacy of VPA. 7,8) However, the total serum VPA concentration is commonly analyzed instead of its unbound concentration in TDM activities, due to the cost-ineffective and time-consuming procedures necessary for measuring the unbound concentration.One approach to evaluate the unbound serum VPA concentration without performing such procedures is to estimate it based on its total serum concentration. In fact, there have been several studies on the estimation and/or a regression equation to predict the unbound from the total concentration.9-11) However, as revealed in our previous study, the equation for epileptic children or adult patients is not applicable for epileptic infants aged less than 1 year old. The unbound serum VPA concentrations in infants vary patient by patient more markedly than those in children, and, thereby, their total and unbound VPA concentrations are poorly correlated (Fig. 1). 12) This means that the unbound VPA concentration in an epileptic infant needs to be directly measured through TDM activities, but he/she is usually so small that it is difficult to draw a volume of blood large enough for measurement. In conjunction with the fact that the adverse reactions of VPA frequently occur in infants, 13,14) it is therefore important to develop an equation to properly estimate the unbound VPA concentration for epileptic infants.To devise such an equation, we chose an empirical approach involving compensating for the equation in children by identifying a factor affecting the unbound VPA concentration. In addition, the parameter to be used for the compensation should be noninvasive, or some measurable value that can be determined without blood drawing. In this study, we The unbound serum concentration of valproic acid (VPA) is closely related to its therapeutic efficacy. In epileptic infants, the unbound VPA concentration varies largely from patient to patient, being difficult to predict using the reported equations for older children. To establish an equation to estimate the unbound concentration in infants, we empirically characterized the relationship between total and unbound VPA concentrations, taking their growth and development into consideration. Data were retrospectively collected fro...

show abstract

“…8 The relatively small muscle mass and decreased muscle blood flow in low birth weight infants may slow the absorption rate of drugs administered by the intramuscular route. 9 Decreased plasma protein binding of drugs 10,11 and sparse amount of body fat in low birth weight infants compared with term infants 12 affects the distribution of lipid-soluble drugs. Similarly, the distribution of water-soluble drugs may be increased in low birth weight infants because of their larger extracellular volume compared with term infants.…”

Section: Nddimentioning

confidence: 99%

The Newborn Drug Development Initiative

Giacoia¹,

Birenbaum²,

Sachs³

et al. 2006

Pediatrics

View full text Add to dashboard Cite

The Best Pharmaceuticals for Children Act (BPCA; Pub L 107-109) was enacted in January 2002 and will sunset in October 2007. The BPCA established processes for studying off-patent and on-patent drugs that are used in pediatric population. Although some drugs have been successfully developed for the neonate (eg, surfactant, nitric oxide), drug development for the youngest, least mature, and most vulnerable pediatric patients is generally lacking. Most drugs are empirically administered to newborns once efficacy has been demonstrated in adults and usefulness is suspected or demonstrated in the older pediatric population. Unfortunately, this process undermines the ability to perform the appropriate studies necessary to demonstrate a drug's short-and long-term safety and efficacy and establish appropriate dosing in neonates. The Newborn Drug Development Initiative Workshop I (held March 29 -30, 2004) specifically addressed scientific, clinical, and ethical concerns in the development of trials of pediatric therapeutic agents for neonates. Implementation of the BPCA for all pediatric populations will foster collaboration among federal agencies and academic institutions on scientific investigation, clinical-study design, and consideration of the weight of evidence and address ethical issues related to the performance of drug studies.www.pediatrics.org/cgi

show abstract

Effects of Development, Aging, and Renal and Hepatic Insufficiency as well as Hemodialysis on the Plasma Concentrations of Albumin and α1-Acid Glycoprotein

Cited by 66 publications

References 0 publications

Plasma protein binding of frusemide in liver disease: effect of hypoalbuminaemia and hyperbilirubinaemia.

Plasma protein binding of frusemide in liver disease: effect of hypoalbuminaemia and hyperbilirubinaemia.

Empirical Approach for Improved Estimation of Unbound Serum Concentrations of Valproic Acid in Epileptic Infants by Considering Their Physical Development

The Newborn Drug Development Initiative

Contact Info

Product

Resources

About