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The Hepatic Sinusoid in Aging and Cirrhosis
- D. Couteur, R. Fraser, S. Kilmer, L. Rivory, A. Mclean
- Medicine, BiologyClinical pharmacokinetics
There is evidence that the sinusoidal changes in cirrhosis and aging contribute to hepatocyte hypoxia, thus providing a mechanism for the apparent differential reduction of oxygen-dependent phase I metabolic pathways in these conditions.
Identification of a new metabolite of CPT-11 (irinotecan): pharmacological properties and activation to SN-38.
- H. Dodds, M. Haaz, J. Riou, J. Robert, L. Rivory
- Chemistry, BiologyThe Journal of pharmacology and experimental…
- 1 July 1998
The structure of CPT-11, a water-soluble derivative of camptothecine with promising activity against several types of malignancies, is postulated to be 7-ethyl-10-(4-amino-1-piperidino)carbonyloxycamptotheCine, and this structure was synthesized by Rhône-Poulenc Rorer.
Pharmacokinetic interrelationships of irinotecan (CPT-11) and its three major plasma metabolites in patients enrolled in phase I/II trials.
- L. Rivory, M. Haaz, P. Canal, F. Lokiec, J. Armand, J. Robert
- MedicineClinical cancer research : an official journal of…
- 1 August 1997
It is concluded that the variability of the pharmacokinetics of CPT-11 and SN-38 is likely to be due to extensive interpatient differences in the pathways implicated in the metabolism of C PT-11.
Imatinib Disposition and ABCB1 (MDR1, P‐Glycoprotein) Genotype
ABCB1 genotype was associated with steady‐state CL/F due to an apparent genotype‐specific influence of imatinib on elimination, and toxicity‐related dose reduction also tended to be less common in these individuals.
Identification and properties of a major plasma metabolite of irinotecan (CPT-11) isolated from the plasma of patients.
7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycampothecin (APC), was further validated following synthesis and was found to be only a weak inhibitor of the cell growth of KB cells in culture.
Metabolism of irinotecan (CPT-11) by human hepatic microsomes: participation of cytochrome P-450 3A and drug interactions.
- M. Haaz, L. Rivory, C. Riché, L. Vernillet, J. Robert
- Biology, ChemistryCancer research
- 1 February 1998
Highly significant correlations are observed between the activity of CPT-11 metabolism into APC and both immunoreactivity with anti-CYP 3A antibodies and testosterone 6beta hydroxylation, an activity specifically mediated by CYP 3A.
Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have an acute-phase response
The reduction in cytochrome P450 3A function with acute-phase reaction was independent of the tumour type and C-reactive protein elevation was associated with poor performance status, which indicates that the sub-group of cancer patients with significant acute- phase response have compromised drug metabolism, which may have implications for the safety of chemotherapy in this population.
Clinical Pharmacokinetics of Docetaxel
Preliminary data suggest the erythromycin breath test, an indicator of CYP3A4 function, is a predictor of toxicity after treatment with docetaxel, and increased doses may be required for patients receiving therapy known to induce this cytochrome (e.g. anticonvulsants).
Conversion of irinotecan (CPT-11) to its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), by human liver carboxylesterase.
Transcriptional Repression of Hepatic Cytochrome P450 3A4 Gene in the Presence of Cancer
- K. Charles, L. Rivory, S. Brown, C. Liddle, S. Clarke, G. Robertson
- Biology, MedicineClinical Cancer Research
- 15 December 2006
A mechanistic link between cancer-associated inflammation and impaired drug metabolism in vivo is provided and targeted therapy to reduce inflammation may provide improved clinical benefit for chemotherapy drugs metabolized by hepatic CYP3A4 by improving their pharmacokinetic profile.