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Alain Durand

Publications and source records attributed to Alain Durand.

8 recordsLinked to original sources
PubMed2004

Retinoids repress Ah receptor CYP1A1 induction pathway through the SMRT corepressor.

CYP1A1 isoform is mainly regulated by the transcription factor AhR and to a lesser extent by the nuclear receptor RAR. The effect of a coexposure with 3MC, a AhR ligand, and RA, a RAR ligand, which are, respectively, strong and weak CYP1A1 inducers, is poorly known. We showed in Caco-2 cells that addition of RA significantly decreased 3MC-induced CYP1A1 expression by -55% for mRNA level and -30% for promoter and enzymatic activities. We further showed that RA decreased AhR protein level. Moreover, a physical interaction between AhR and the RAR-corepressor SMRT has been described in vitro. Using the corepressor inhibitor TSA, transfected-cells with SMRT cDNA, and coimmunoprecipitation experiments, we demonstrated that RA addition repressed AhR function through a marked AhR/SMRT physical interaction. This interaction explains the decrease of 3MC-induced CYP1A1 expression. This new mechanism involving the repression of AhR-induced CYP1A1 expression by retinoids allows better knowledge of the CYP1A1 regulation.

Caco-2 Cells↗
PubMed2004

Therapeutic drug monitoring of lopinavir/ritonavir given alone or with a non-nucleoside reverse transcriptase inhibitor.

AIMS: To evaluate the interindividual variability in the plasma concentrations of lopinavir in the context of routine monitoring with or without treatment with a non-nucleoside reverse transcriptase inhibitor and to assess the interaction between the coformulation of lopinavir/ritonavir and efavirenz or nevirapine. METHODS: Plasma trough and peak concentrations (C(trough), C(max)) of lopinavir from 182 HIV-1-infected patients were analysed by high-performace liquid chromatography. Three lopinavir/ritonavir regimens were assessed, namely (A) 400 mg lopinavir/100 mg ritonavir twice daily given alone (n = 125), (B) 400/100 mg twice daily together with a non-nucleoside reverse transcriptase inhibitor (n = 25), and (C) 533/133 mg twice daily together with a non-nucleoside reverse transcriptase inhibitor (n = 32). RESULTS: Median (ng ml(-1)) C(trough) and C(max) lopinavir (interquartile range, CV) were: (A) 4852 (3198-6891, 56%) and 8501 (6333-11 584, 41%), (B) 2979 (1704-5186, 74%) and 5612 (3362-11 704, 76%) and (C) 5082 (2696-7226, 74%) and 9757 (4883-12 963, 60%). Median C(trough) of lopinavir was lower in patients taking both efavirenz [P = 0.01, 95% confidence interval (CI) for difference between medians 343, 2713] and nevirapine (P = 0.019, 95% CI for difference between medians 354, 3681) compared with those taking lopinavir/ritonavir alone. A higher interindividual variability was observed when lopinavir/ritonavir was given with a non-nucleoside reverse transcriptase inhibitor. The risk of achieving a 'suboptimal'C(trough) of lopinavir (below a threshold of 3000 ng ml(-1)) was statistically higher in patients treated with a non-nucleoside reverse transcriptase inhibitor (P < 0.001, 95% CI for difference between percentages 8.8, 43.1%) compared with those receiving lopinavir/ritonavir alone. CONCLUSIONS: Our results confirmed the interaction between lopinavir and efavirenz, and also demonstrated a significant interaction between the former drug and nevirapine, resulting in lower C(trough) of lopinavir. The wide interpatient variability in this interaction suggests that therapeutic drug monitoring may be useful in optimizing the dose of lopinavir.

Adolescent↗
PubMed2003

Jamin Fabry-Perot interferometer.

A novel type of interferometer was designed and tested experimentally. It combines the advantages of the spatial path separation used in the two-wave polarized Jamin interferometer and the high sensitivity that characterizes the multiwave Fabry-Perot interferometer. Furthermore, when it is sandwiched between crossed polarizers it shows a sensitivity to intracavity anisotropies that is proportional to the square of the Fabry-Perot interferometer's finesse.

Journal Article↗
PubMed2002

High indinavir Cmin is associated with higher toxicity in patients on indinavir-ritonavir 800/100 mg twice-daily regimen.

We retrospectively evaluated the incidence of side effects and treatment intervention according to indinavir trough concentration in 63 patients taking indinavir-ritonavir 800/100 mg twice daily. Median indinavir trough concentration was 1446 ng/mL at 800/100 mg twice daily associated with 60% of measured toxicity. Among patients with indinavir trough concentration >500 ng/mL, 46 of 49 had a dosage adjustment and 17 have had more than two dosage adjustments. The primary reason for dosage adjustment was toxicity in 69% (43 cases). Renal and cutaneous toxicity were predominant.After dosage adjustment, median indinavir trough concentration was 459 ng/mL, which was associated with 8% of toxicity. Trough concentrations >500 ng/mL were correlated with increased toxicity (p <.05) and more treatment intervention (p =.02). In conclusion, achievement of indinavir trough concentrations <500 ng/mL appears to be safe, and an optimal concentration range for indinavir trough concentration could be 150 to 500 ng/mL for an indinavir-ritonavir twice daily regimen.

Adult↗
PubMed2002

Increase of CYP1B1 transcription in human keratinocytes and HaCaT cells after UV-B exposure.

Nonmelanoma skin cancers represent the most common malignant neoplasms in humans. UV-B play a major role in the etiology of these tumors, but exposure to environmental procarcinogens is also involved. CYP catalyzes numerous chemical carcinogen bioactivations and effects of UV-B on their expression are poorly understood. The aim of this study was to explore the molecular events involved in the induction of CYP1B1, a major cutaneous CYP, by UV-B. Our results demonstrated that unique UV-B exposure (20 mJ/cm(2)) increases human CYP1B1 transcript in primary keratinocytes and HaCaT cell cultures. Among 20 human samples studied, we observed a large interindividual variability of CYP1B1 mRNA induction (1.1- to 4.5-fold). Pretreatment with an antioxidant, N-acetylcysteine, repressed CYP1B1 increase, suggesting the involvement of UV-B photoproducts. alpha-Amanitin inhibition studies and CAT assays demonstrated that CYP1B1 mRNA induction is associated with a transcriptional activation of its expression. alpha-Naphthoflavone inhibition studies and CAT assays performed after directed mutagenesis of xenobiotic responsive element sites showed the involvement of Ah receptor. Taken together, these data demonstrated that UV-B induces CYP1B1 gene expression after an activation of its transcription, which involves Ah receptor.

Amanitins↗
PubMed2002

Brain tissue penetration of ciprofloxacin following a single intravenous dose.

Ciprofloxacin distribution was assessed in cerebral tissues in 14 patients undergoing craniotomy. The study objective was to determine the brain tissue/serum concentration ratio of ciprofloxacin. Patients received a single intravenous (iv) 200 mg dose of ciprofloxacin. Mean (+/- S.D.) tissue/serum concentration ratios were (mg/kg): parietal fat during opening 1.40 +/- 1.05, during closure 1.34 +/- 1.17, in the dura mater 2.26 +/- 1.36, in skull bone during opening 0.44 +/- 0.29, during closure 0.97 +/- 1.57 and in brain tissue 0.88 +/- 0.99. Mean (+/- S.D.) concentrations of ciprofloxacin in brain tissue were 0.87 +/- 0.08 mg/kg, suggesting that a dose >200 mg iv ciprofloxacin is required to ensure therapeutic concentrations in brain tissue.

Adult↗
PubMed2002

Population pharmacokinetics of etoposide: application to therapeutic drug monitoring.

Antineoplastic agent etoposide (VP16) displays narrow therapeutic index and erratic pharmacokinetics, and dose individualization is a convenient way for overcoming the interpatient variability, so as to maintain the drug exposure within a therapeutic range. The authors proposed a population-based Bayesian methodology to adjust routinely VP16 dosage when given as a 5-day infusion. The mean VP16 pharmacokinetic parameters of the reference population calculated from 14 patients following the two-stage method were CL = 1.92 +/- 0.512 L/h and t(1/2) = 6.7 +/- 2 hours. The reference population was next used prospectively for Bayesian dose individualization for 25 patients (47 courses) undergoing 5-day infusions of VP16. Resulting steady-state concentrations proved to be successfully adjusted to the target values in 77% of the courses. Therefore, the method presented here meets the requirements for routine therapeutic drug monitoring of VP16, a major anticancer drug extensively used in clinical oncology.

Adult↗