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BACKGROUND Hyperthermic intraperitoneal intraoperative chemotherapy (HIIC) combined with cytoreductive surgery (CS) has been proposed as a new multimodal treatment mainly for carcinomatosis of gastrointestinal origin. To evaluate whether this regimen could be used for other tumor types, the authors conducted a Phase I study on HIIC with doxorubicin and(More)
We evaluated the effects of increasing concentrations of the flavonoids salvigenin, diosmetin and luteolin on the in vitro metabolism of midazolam (MDZ), a probe substrate for cytochrome P450 (CYP) 3A enzymes, which is converted into 1'-hydroxy-midazolam (1'-OH-MDZ) and 4-hydroxy-midazolam (4-OH-MDZ) by human liver microsomes. Salvigenin had only a modest(More)
BACKGROUND Plasma creatinine concentration and calculated creatinine clearance are of limited value as glomerular filtration rate (GFR) markers in patients with decompensated liver cirrhosis. We assessed plasma cystatin C as an indicator of GFR in such patients. METHODS We studied 36 patients with decompensated liver cirrhosis and 56 noncirrhotic(More)
Intraperitoneal chemotherapy, mainly when performed during HIIC after cytoreductive surgery, is considered potentially curative for the treatment of solid tumors with spread to the peritoneal surface. When selecting antiblastic agents to be administered intraperitoneally, it is important to bear in mind that a low lipophility and a high molecular weight are(More)
A combination of tacrolimus (TAC) and sirolimus (SIR) has recently proved to be a very effective immunosuppressive regimen in organ transplantation. In pediatric transplant recipients, co-administration of these two drugs has been shown to result in a significant decrease of exposure to TAC, whereas conflicting data have been obtained regarding this(More)
Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a natural phytoalexin found in grapes and wine. It has antioxidant and antiproliferative activities, and has been shown to induce NAD(P)H:quinone oxidoreductase, also known as DT-diaphorase, in cultured mouse hepatoma cells. DT-diaphorase is a detoxifying enzyme for quinone-containing substances, due to its(More)
The aim of this study was to examine in vitro, by means of kinetic analysis and molecular docking simulations, the effects of the flavone diosmetin and its flavanone analog hesperetin on CYP (cytochrome P450) 2C9-mediated drug metabolism. To this purpose, the conversion of diclofenac to 4'-hydroxydiclofenac by human liver microsomes was used as a model(More)
We recently demonstrated that nemorubicin (MMDX), an investigational antitumor drug, is converted to an active metabolite, PNU-159682, by human liver cytochrome P450 (CYP) 3A4. The objectives of this study were: (1) to investigate MMDX metabolism by liver microsomes from laboratory animals (mice, rats, and dogs of both sexes) to ascertain whether PNU-159682(More)
BACKGROUND AND OBJECTIVES In vivo inhibition of cytochrome P450 (CYP) 1A2 by fluvoxamine causes a reduction in the clearance of the high-extraction drug lidocaine, which decreases in proportion to the degree of liver dysfunction. The objectives of this study were (1) to evaluate the effect of liver cirrhosis on the inhibition by fluvoxamine of the metabolic(More)
This article reviews the influence of liver functional status on pharmacokinetic interactions due to inhibition and induction of drug-metabolizing enzymes. Recent human studies have shown that the magnitude of inhibitory interactions caused by the reversible CYP1A2 inhibitor fluvoxamine decreases as liver function worsens, and virtually vanishes in patients(More)