Drug binding defect of uraemic plasma: Unlikely involvement of carbamoylated albumin

Clegg, L. S.; Lindup, W E

doi:10.1016/0006-2952(82)90134-4

Cited by 9 publications

(1 citation statement)

References 23 publications

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“…In diabetes mellitus, renal failure and alcoholism, an in crease of glycosylated [1], carbamoylated [2] and acetaldehyde modified [3] haemoglobin has been described and, more recently, the non-enzymatic modification of serum pro teins has also been reported [4][5][6], It was therefore of interest to determine if the func tional properties of proteins such as drug binding could be altered. Such investigations were previously carried out for glycosylated albumin [7] and carbamoylated plasma pro teins [5,8].…”

Section: Introductionmentioning

confidence: 99%

Acetaldehyde Adducts with Serum Proteins: Effect on Diazepam and Phenytoin Binding

Lucas¹,

Ménez²,

Daniel³

et al. 1986

Pharmacology

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The in vitro effects of acetaldehyde treatment on the binding of phenytoin and diazepam to human serum albumin (HSA) and human serum proteins (HSP) have been investigated. The incorporation of acetaldehyde into proteins following incubation with different concentrations of [1, 2–14 C]-acetaldehyde (0.5, 25, 100 mmol/l) was carried out. The proteins were then dialyzed so that only the stable adduct was retained. Binding of phenytoin and diazepam was then studied. Scatchard plot analysis showed a slight decrease (p < 0.01 for HSP and 25 mmol/l acetaldehyde) in the number of binding sites for phenytoin when the acetaldehyde/protein ratio was increased. The affinity constant was also increased (p < 0.01) with 100 mmol/l acetaldehyde. No change could be demonstrated in the number of diazepam binding sites on HSA; an increase in the binding capacity of HSP was shown following incubation with 25 mmol/l acetaldehyde. The fraction of drug bound at therapeutic levels has been also calculated for both drugs. An increase for diazepam but no change for phenytoin can be observed before or after treatment of proteins with acetaldehyde.

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Section: Introductionmentioning

confidence: 99%

Acetaldehyde Adducts with Serum Proteins: Effect on Diazepam and Phenytoin Binding

Lucas¹,

Ménez²,

Daniel³

et al. 1986

Pharmacology

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Urea Metabolism: Clinical Chemistry of Urea

Depner

1991

Prescribing Hemodialysis

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Pharmacokinetic effects of altered plasma protein binding of drugs in renal disease

Keller

Maïga

Neumayer

et al. 1984

European Journal of Drug Metabolism and Pharmacokinetics

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The measurement of plasma drug concentrations provides no insight into the relationship between the free and the plasma-protein-bound fractions of drugs. Plasma protein binding may decrease in renal disease due to uremia, hypoalbuminemia, or due to drug interactions. Decreased plasma protein binding leads to an increase in free plasma fraction causing an increase in volume of distribution and a shorter elimination half life. The increase in the apparent volume of distribution and the shorter elimination half life cause a decrease in total plasma concentration. Therefore, the free drug concentration is more reliable than the total plasma concentration for therapeutic drug monitoring. However, the free amount in plasma and in tissue and the tissue-bound amount remain unchanged under steady state conditions. Thus, a decrease in plasma protein binding in renal disease usually does not lead to increased drug toxicity, and alteration of drug dosage is not required, although the total plasma concentration may be found to be considerably lower than normal. In addition to plasma protein binding, alteration of tissue binding must also be considered for the determination of the appropriate dosage of some drugs in renal disease.

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Drug binding defect of uraemic plasma: Unlikely involvement of carbamoylated albumin

Cited by 9 publications

References 23 publications

Acetaldehyde Adducts with Serum Proteins: Effect on Diazepam and Phenytoin Binding

Acetaldehyde Adducts with Serum Proteins: Effect on Diazepam and Phenytoin Binding

Urea Metabolism: Clinical Chemistry of Urea

Pharmacokinetic effects of altered plasma protein binding of drugs in renal disease

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