Docetaxel serum protein binding with high affinity to alpha1-acid glycoprotein

  title={Docetaxel serum protein binding with high affinity to alpha1-acid glycoprotein},
  author={Sa{\"i}k Urien and J{\'e}r{\^o}m{\'e} Barr{\'e} and Christophe Morin and Anne J Paccaly and Guy Montay and Jean Paul Tillement},
  journal={Investigational New Drugs},
SummaryThe binding of docetaxel to human plasma proteins was studied by ultrafiltration at 37°C and pH 7.4. Docetaxel was extensively (> 98%) plasma protein bound. At clinically relevant concentrations (1–5 μg/ml), the plasma binding was concentration-independent. Lipoproteins, alpha1-acid glycoprotein and albumin were the main carriers of docetaxel in plasma, and owing to the high interindividual variability of alpha1-acid glycoprotein plasma concentration, particularly in cancer, it was… 
Spectroscopic characterization of Docetaxel binding to human serum albumin
The probe here developed could be applied to evaluate Docetaxel-HSA binding in di erent formulations and concluded that the best conditions to evaluateDocetaxe-Hsa interaction are: 4 to 28μM of Docetxel, 2 μM protein, without incubation of reagents, and using a 0.5 cm path length.
Pharmacokinetics and pharmacodynamics of protein‐unbound docetaxel in cancer patients
Pharmacokinetics of unbound drug rather than total drug is a better predictor of neutropenia for docetaxel.
In vitro partition of docetaxel and gemcitabine in human volunteer blood: the influence of concentration and gender
It is concluded that the incorporation of drugs into the RBC pool may be important for transportation to tumor tissue and efficacy, and in combination, one anti-cancer agent can alter the partition ratios of other anti- cancer agents.
The effects of advanced age and serum α1‐acid glycoprotein on docetaxel unbound exposure and dose‐limiting toxicity in cancer patients
Serum AAG level and ANC at baseline appear to be predictive of neutropenia for patients of all ages following the administration of docetaxel, regardless of ageing.
In Vitro Binding and Partitioning of Irinotecan (CPT-11) and its Metabolite, SN-38, in Human Blood
The binding of CPT-11 and SN-38 to human plasma proteins was studied by ultrafiltration at 37°C and pH 7.4 and albumin was the main carrier ofCPT-11 in plasma.
Limited cerebrospinal fluid penetration of docetaxel
The data suggest that measurement of unbound docetaxel is required to accurately assess the extent of drug penetration into CSF and that the drug can produce distribution to CSF at levels associated with significant antitumor activity in experimental models.
Can alpha-1-acid glycoprotein affect the outcome of treatment in a cancer patient?
The role of increased AGP levels in cancer patients is discussed and the role of AGP as a drug-binding protein and its effect on the efficacy of chemotherapy in oncological patients is dealt with.
Dexamethasone as a probe for CYP3A4 metabolism: evidence of gender effect
Dexamethasone may be used to predict docetaxel clearances in females, but not in males; however, after splitting of the prospective data set according to gender, no correlation was observed for males, and strong correlation for females.


Binding of taxol to human plasma, albumin and alpha 1-acid glycoprotein.
The protein binding ofTaxol was found to dramatically decrease the red blood cell uptake of taxol, indicating nonspecific hydrophobic binding.
Role of alpha‐1 acid glycoprotein, albumin, and nonesterified fatty acids in serum binding of apazone and warfarin
It is strongly suggested that when hypoalbuminemia is present and a drug binds to AAG with an affinity constant comparable to or higher than that to albumin, then fu will become dependent on the concentration of AAG.
Binding of indapamide to serum proteins and erythrocytes.
Effects of cancer and its treatments on plasma concentration of alpha1‐acid glycoprotein and propranolol binding
The data imply that untreated or unsuccessfully treated cancer patients will have reduced free fractions for any drug for which AAG is an important binding protein, and successfully treated patients may have longitudinal changes towards normal.
Methadone plasma protein binding: Alterations in cancer and displacement from α1‐acid glycoprotein
  • F. Abramson
  • Biology
    Clinical pharmacology and therapeutics
  • 1982
The concentrations required for significant displacement (27 μM), as well as the relatively low Ka for methadone, suggest that the free fraction of methadon will not be significantly affected by elevated methamphetamine concentrations or through displacement by other drugs that also bind to AAG.
The plasma protein binding of basic drugs.
  • P. Routledge
  • Medicine, Biology
    British journal of clinical pharmacology
  • 1986
The plasma protein binding of basic drugs appears to vary more than was at first assumed and is related to the marked intra-and interindividual differences in one of the chief binding proteins, AAG.
Determinants of plasma alpha 1-acid glycoprotein (AAG) concentrations in health.
It is concluded that in addition to the known effects of age and gender, environmental (rather than genetic) factors largely determine the variance of AAG concentrations.
Pharmacokinetics and metabolism of Taxotere (docetaxel).
The pharmacokinetics and metabolism of Taxotere have been studied after intravenous infusion in mice, dogs and cancer patients and large scale prospective population pharmacokinetic/pharmacodynamic studies have been implemented in ongoing phase II studies.
The taxoids: paclitaxel (Taxol) and docetaxel (Taxotere).
The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum.
The relatively low density of the lipoproteins was utilized by Lindgren, Elliott, and Gofman to separate them from the other serum proteins by ultracentrifugal flotation, and quantitation was subsequently performed by refractometric methods in the analytical ultracentRifuge.