Prediction of exposure-driven myelotoxicity of continuous infusion 5-fluorouracil by a semi-physiological pharmacokinetic-pharmacodynamic model in gastrointestinal cancer patients.

Purpose: To describe 5-fluorouracil (5FU) pharmacokinetics, myelotoxicity and respective covariates using a simultaneous nonlinear mixed effect modelling approach.

Methods: Thirty patients with gastrointestinal cancer received 5FU 650 or 1000 mg/m/day as 5-day continuous venous infusion (14 of whom also received cisplatin 20 mg/m/day). 5FU and 5-fluoro-5,6-dihydrouracil (5FUH2) plasma concentrations were described by a pharmacokinetic model using NONMEM.

Drug cocktail interaction study on the effect of the orally administered lavender oil preparation silexan on cytochrome P450 enzymes in healthy volunteers.

Unlabelled: This cocktail study evaluated the interaction potential of the oral lavender oil preparation silexan with major P450 (cytochrome P450) enzymes.

Subjects And Methods: Sixteen healthy male or female Caucasians completed this double-blind, randomized, 2-fold crossover study. Silexan (160 mg) or placebo were administered once daily for 11 days.

Profiling of mercapturic acids of acrolein and acrylamide in human urine after consumption of potato crisps.

Scope: Acrolein (AC) and acrylamide (AA) are food contaminants generated by heat treatment. We studied human exposure after consumption of potato crisps by monitoring excretion of mercapturic acids (MAs) in urine.

Methods And Results: MA excretion was monitored in human urine collected up to 72 h after ingestion of a test meal of experimental (study 1: 1 mg AA/150 g) or commercially available (study 2: 44 μg AA plus 4.

Clinical pharmacokinetics of tyrosine kinase inhibitors: focus on pyrimidines, pyridines and pyrroles.

Pyrimidine (imatinib, dasatinib, nilotinib and pazopanib), pyridine (sorafenib) and pyrrole (sunitinib) tyrosine kinase inhibitors (TKIs) are multi-targeted TKIs with high activity towards several families of receptor and non-receptor tyrosine kinases involved in angiogenesis, tumour growth and metastatic progression of cancer. These orally administered TKIs have quite diverse characteristics with regard to absorption from the gastrointestinal tract. Absolute bioavailability in humans has been investigated only for imatinib (almost 100%) and pazopanib (14-39%; n = 3).

Clinical pharmacokinetics of tyrosine kinase inhibitors: focus on 4-anilinoquinazolines.

The 4-anilinoquinazolines (gefitinib, erlotinib and lapatinib) are members of a class of potent and selective inhibitors of the human epidermal growth factor receptor (HER) family of tyrosine kinases that have been developed to treat patients with tumours with defined genetic alterations of the HER tyrosine kinase domain. They are characterized by a moderate rate of absorption after oral administration with peak plasma concentrations at several hours post-dose. Absolute bioavailability of gefitinib and erlotinib is about 60%.