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

Urien, Saı̈k; Barré, Jérôme; Morin, Christophe; Paccaly, Anne; Montay, G.; Tillement, Jean‐Paul

doi:10.1007/bf00210785

Cited by 103 publications

(94 citation statements)

References 7 publications

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“…Increased AAG resulted in a decreased Slope value. This relationship was also expected since docetaxel is extensively bound to AAG, and this is mainly responsible for interindividual variability in docetaxel unbound fraction (f u ) (Urien et al, 1996). In the present NONMEM analysis, the Slope values link total plasma docetaxel concentrations and neutropaenic responses.…”

Section: Discussionsupporting

confidence: 52%

“…However, the relationship between the Slope values and the AAG level does not lead to dosing recommendations based on the AAG level. Indeed, several studies have confirmed that the docetaxel CL is dependent on f u , with a lower CL in patients with high AAG levels (Urien et al, 1996;Baker et al, 2005). Interindividual variability in AAG is not associated with marked changes in the AUC of free docetaxel.…”

Section: Discussionmentioning

confidence: 95%

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Clinical pharmacodynamic factors in docetaxel toxicity

et al. 2007

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Neutropenia is the main dose-limiting toxicity occurring in docetaxel treatment. The objective of this study was to identify pharmacodynamic (PD) factors responsible for the neutropaenia caused by docetaxel. Data were obtained from 92 patients treated with docetaxel as a monochemotherapy in two different treatment centres. A semiphysiological population pharmacokineticpharmacodynamic (PK/PD) model was applied to describe the time course of neutrophils and the neutropaenic effect of docetaxel. The plasma docetaxel concentration was assumed to inhibit the proliferation of neutrophil precursors through a linear model: Drug effect ¼ Slope Â Conc. Slope corresponds to the patients' sensitivity to the neutropaenic effect of docetaxel. Covariate analysis was performed by testing the relationship between the patients' characteristics and Slope using the program NONMEM. The neutropaenic effect of docetaxel showed a high interindividual variability. Three significant PD covariates were identified: serum a1-acid glycoprotein levels (AAG), level of chemotherapy pretreatment, and treatment centre. Extensive pretreatment was associated with an increase in Slope values meaning a higher haematotoxicity. An increase in AAG was associated with a decrease of both Slope and docetaxel plasma clearance. Patients treated in one centre had both higher Slope and docetaxel clearance. The centre effect (most likely due to a bias in the PK part of the study between the two centres) reveals the robustness of the PK/PD model. Individual dosing of docetaxel should be based on previous chemotherapy but not on the AAG level since it has a similar influence on PD and PK docetaxel parameters. This methodology should be applied to further investigate elderly patients and to identify more precisely the characteristics of previous chemotherapy that contribute to the cumulative myelotoxicity.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 95%

Clinical pharmacodynamic factors in docetaxel toxicity

et al. 2007

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“…The one-step LLE was proved to be simple, rapid and successful with an average recovery ratio of about 89-91% for docetaxel at the tested concentrations Table 2 Recovery of docetaxel was found to be less as the drug is highly protein bound (~ 97%). 8,9 Hence the % RSD for recoveries was found to be all below 8%. The possibility of matrix effect caused by ionization competition between the analytes and the endogenous co-eluents was evaluated at three QC concentrations in triplicate.…”

Section: Recovery and Matrix Effectmentioning

confidence: 92%

A Rapid and Sensitive Bio Analytical RP-HPLC Method for Detection of Docetaxel: Development and Validation

Kharkar¹,

Talkar²,

Patravale³

2017

IJPER

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Objective: A rapid and selective high-performance liquid chromatographic (HPLC) method has been developed and validated for Docetaxel anhydrous (DTX) using Ketoconanzole (KCZ) as an internal standard in biological fluids. Methods: The analyte was extracted from human plasma by liquid-liquid extraction method using acetonitrile. The analysis was carried out on Licrosphere IV, C 8 column (LC-GC Chromatography Solutions Pvt. Ltd, Mumbai, and India) (4.6×250 mm) with isocratic elution using a mobile phase composition of 0.2% triethylamine (pH 6.4 with orthophosphoric acid) (45%) and Acetonitrile (55%). The flow rate was 1.5ml/min with absorbance wavelength of 230 nm. Results: The developed method was found to be linear over the range of 100-2500 ng/mL with correlation coefficients of about 0.999. The limit of quantification for docetaxel was found to be 100 ng/mL. The limit of detection was found to be 50 ng/ mL. The intra-and inter-day precision was determined to be <5% and the accuracy was 99-105%. The overall recovery for docetaxel was about 89.0% -91.0%. The total analysis time was only 10.0 min. The method was successfully applied for determination of DTX in rat plasma, to establish the pharmacokinetic profile of a marketed formulation. Conclusion: A simple, sensitive, rapid, accurate and prudent RP-HPLC method was developed, validated and applied for the Docetaxel anhydrous.

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“…The plasma protein binding rate of docetaxel was >90%, while that of thio-TEPA was <15%; docetaxel rarely passes through the renal corpuscle, while thio-TEPA is easily excreted. 19,20 Docetaxel or thio-TEPA dissolved in DMEM with 10% FBS was circulated throughout the circulation channel to assay its anticancer activity with the system.…”

Section: Bioassay Of Anticancer Agents With the Systemmentioning

confidence: 99%

Development of a Multichannel Dialysis Microchip for Bioassay of Drug Efficacy and Retention

2017

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Here, we developed a multichannel dialysis microchip having three sets of dialysis systems, which consisted of three independent circulation channels with a common micropump. Each dialysis system was composed of a pneumatic micropump (heart), dialysis unit (renal corpuscle), and cell culture chamber (drug target) as well as circulation and dialysate channels to mimic the circulation system. Small molecules were successfully separated in parallel from macromolecules at the dialysis components. Anticancer tests using this microchip showed results that considered both serum protein-binding nature and drug activity. In the anticancer bioassay, the multichannel chip showed similar reproducible and reliable results as those of the single-channel system but with higher throughput.

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

Cited by 103 publications

References 7 publications

Clinical pharmacodynamic factors in docetaxel toxicity

Clinical pharmacodynamic factors in docetaxel toxicity

A Rapid and Sensitive Bio Analytical RP-HPLC Method for Detection of Docetaxel: Development and Validation

Development of a Multichannel Dialysis Microchip for Bioassay of Drug Efficacy and Retention

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