The binding of ketamine to plasma proteins: Emphasis on human plasma

@article{Dayton2004TheBO,
  title={The binding of ketamine to plasma proteins: Emphasis on human plasma},
  author={Peter G. Dayton and Richard L. Stiller and David R. Cook and James M. Perel},
  journal={European Journal of Clinical Pharmacology},
  year={2004},
  volume={24},
  pages={825-831}
}
SummaryWe report for the first time that ketamine (K) is bound as much as 47% to human plasma. It was shown that binding of K to plasma and albumin is dependent on pH; binding is decreased at pH lower than 7.4 and increased at higher pH. This is in concordance with the pKa of K being 7.5; the partition coefficient between an organic phase and buffer was found to be sensitive to small pH changes. Binding of K is also influenced by albumin concentration and the affinity of K for human α1-acid… 
Protein binding of ketamine and its active metabolites to human serum
TLDR
The percentage of drug bound to serum proteins at 30°C was found to be 69%, 60% and 50% for DHNK, ketamine and NK, respectively, while these percentages were 75%, 64% and 54% forDHNK, NK and NK respectively at 20°C.
Propofol increases the rate of albumin-unbound free midazolam in serum albumin solution
TLDR
The findings suggest that the increase in albumin-unbound free midazolam brought about by propofol is involved in the synergistic effect of these two agents.
Stereoselectivity of the binding of drugs by blood plasma proteins (review)
TLDR
Although the pharmacological and clinical significance of the binding of drugs by serum or plasma proteins has been widely discussed for more than 40 years, the aspects of the stereo-specificity of this interaction have been developed only during the last 15 years.
Effects of enzyme induction, renal and cardiac function on ketamine plasma kinetics in patients with ketamine long-term analgosedation
TLDR
Steady-state plasma levels of ketamine and its metabolites norketamines and dehydronorketamine were determined in 4 different groups of a total of 27 patients with ketamine long-term analgosedation and psychomimetic effects could be excluded in 16 of the patients and were unlikely in 6 patients.
Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy
TLDR
Well-known psychotomimetic and cognitive adverse effects restrict the clinical usefulness of ketamine, even though fewer psychomimetic adverse effects have been reported with S-ketamine in comparison with the racemate.
Pharmacokinetics and non-analgesic effects of S- and R-ketamines in healthy volunteers with normal and reduced metabolic capacity
TLDR
There are large differences between arterial and venous data in the pharmacokinetic parameters that are heavily dependent on distribution processes in low-dose ketamine.
PROTEIN BINDING OF DRUGS, DRUG ENANTIOMERS, ACTIVE DRUG METABOLITES AND THERAPEUTIC DRUG MONITORING
TLDR
This chapter is initially to discuss studies comparing unbound and total drug concentration monitoring with intensity of effect to see how much clinical utility is really gained by introducing the extra analytical step necessary to measure free drug concentrations.
CYP2B6*6 allele and age substantially reduce steady-state ketamine clearance in chronic pain patients: impact on adverse effects.
TLDR
The CYP2B6*6 allele is associated with a substantial decrease in steady-state ketamine plasma clearance in chronic pain patients and the decreased clearance and resultant higher plasma concentrations may beassociated with a higher incidence of ketamine adverse effects.
Metabolism and metabolomics of ketamine: a toxicological approach
TLDR
Knowing the metabolism and metabolomics of ketamine may provide further insights aiming to better characterize ketamine from a clinical and forensic perspective.
Subanesthetic Ketamine Does Not Affect 11C-Flumazenil Binding in Humans
TLDR
PET studies suggest that propofol and inhaled anesthetics increase 11C-flumazenil binding in the living human brain, thus supporting the involvement of &ggr;-aminobutyric acid type A (GABAA) receptors in the mechanism of action of these drugs.
...
...

References

SHOWING 1-10 OF 52 REFERENCES
Disease-induced Changes in the Plasma Binding of Basic Drugs
  • K. Piafsky
  • Biology, Medicine
    Clinical pharmacokinetics
  • 1980
TLDR
Plasma concentration monitoring of drug therapy by use of total drug concentrations will be inaccurate in situations in which large variations in binding occur, and misinterpretations of both therapeutic monitoring and pharmacokinetic studies in disease slates with altered binding are likely.
Plasma protein binding of basic drugs
TLDR
Drug binding, however, did not correlate with albumin concentration, although experiments with isolated albumin demonstrated its unusually high affinity for naproxen, which confirms recent experiments which showed that isolated ai‐acid glycoprotein avidly bound both alprenolol and imipramine.
Increased plasma protein binding of propranolol and chlorpromazine mediated by disease-induced elevations of plasma alpha1 acid glycoprotein.
TLDR
Increases in plasma protein binding in patients with inflammatory disease appear mediated by increases in alpha1 acid glycoprotein concentration, which may influence drug kinetics.
Meperidine binding in maternal and fetal plasma
  • R. Nation
  • Medicine
    Clinical pharmacology and therapeutics
  • 1981
TLDR
Plasma binding of this basic drug was not greatly influenced by the perinatal levels of bilirubin and nonesterified fatty acids, and a relatively large proportion of the overall variability in B/F was accounted for by plasma α1‐AGP and albumin.
Plasma protein binding of phencyclidine
TLDR
Increased plasma protein binding can reduce free drug concentration during the distribution phase and, thereby, the rate and extent of drug distribution, demonstrating that increased plasma proteinbinding can reduceFree drug concentration in plasma over HSA and in patients with mild to moderate alcoholic liver disease.
Plasma protein binding of basic drugs. I. Selective displacement from alpha 1-acid glycoprotein by tris(2-butoxyethyl) phosphate.
TLDR
The plasticizer tris(2-butoxyethyl) phosphate (TBEP), present in plasma collected in Vacutainers, was a potent inhibitor of alprenolol and imipramine protein binding, and its concentration in the plasma could quantitatively explain the displacement phenomenon.
Binding of perazine to alpha 1-acid glycoprotein.
TLDR
It was demonstrated by equilibrium dialysis that the average free fraction of 3H-perazine added to 22 sera from patients before neuroleptic treatment was 3.67 +/- 0.42%, and that there was a significant correlation between the alpha 1-acid glycoprotein content and the free fraction in these serum samples.
On the cerebral accumulation of ketamine and the relationship between metabolism of the drug and its pharmacological effects.
  • M. Cohen, A. Trevor
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1974
TLDR
Determination of the partition coefficients of ketamine and its N-demethylated product (metabolite I) indicated that both compounds were highly lipid soluble which may account for their rapid accumulation by cerebral tissues.
Alpha1‐acid glycoprotein concentration and protein binding in trauma
TLDR
Findings with drugs commonly used in trauma patients would be expected to alter serum concentration‐response relationships significantly.
Changes in plasma drug binding and alpha 1-acid glycoprotein in mother and newborn infant.
  • M. Wood, A. Wood
  • Medicine, Biology
    Clinical pharmacology and therapeutics
  • 1981
TLDR
There was a positive correlation between plasma alpha 1-acid glycoprotein concentrations and the binding ratio (bound/free concentrations) of lidocaine and propranolol, indicating that it is likely that the elevation of the free fraction of these drugs in the fetus is due in part to lower levels of alpha 2-acid Glycoprotein.
...
...