A phase IB clinical and pharmacokinetic study of the angiogenesis inhibitor SU5416 and paclitaxel in recurrent or metastatic carcinoma of the head and neck.

Purpose: SU5416 is a novel small organic molecule that non-competitively inhibits the phosphorylation of the VEGF tyrosine kinase receptor, Flk-1. This phase IB study was performed to determine the safety, pharmacokinetics, and preliminary efficacy of the combination of SU5416 and paclitaxel in recurrent or metastatic carcinoma of the head and neck.

Methods: Enrolled in the study were 12 patients with biopsy-proven recurrent or metastatic carcinoma of the head and neck.

Prevention of tricyclic antidepressant adsorption loss with diethylamine during solvent evaporation.

The authors evaluated the adsorption loss of tricyclic antidepressants in analytical procedures with solvent extraction and evaporation. In standard procedures with the use of triple solvent extraction between alkalinized and acidified samples before chromatographic analysis, the adsorption loss was more significant with the demethylated metabolites. As much as 50% adsorption loss can occur; this irreversible loss can be accounted for entirely during the solvent evaporation step.

Inhibition of mitochondrial respiration by analogues of the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium: structural requirements for accumulation-dependent enhanced inhibitory potency on intact mitochondria.

Analogues of 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, were evaluated for inhibition of respiration in intact mitochondria (Mw) and in electron transport particles (ETP). MPP+ exhibits relatively weak inhibitory activity in ETP, but potent inhibition in Mw occurs on account of its energy-dependent accumulation inside mitochondria. The permeant anion tetraphenylborate potentiates the inhibition in both Mw and ETP.