Phase I trial of tirapazamine and cyclophosphamide in children with refractory solid tumors: a pediatric oncology group study.

Purpose: To determine the dose limiting toxicity (DLT), maximum-tolerated dose (MTD), and pharmacokinetic profile of tirapazamine (Sanofi Synthelabo Research, Malvern, PA) combined with cyclophosphamide in children with recurrent solid tumors.

Patients And Methods: Patients received a 2-hour infusion of tirapazamine, followed by 1,500 mg/m(2) cyclophosphamide, and mesna once every 3 weeks. Dose escalation of tirapazamine began at 250 mg/m(2) and was increased by 30% in subsequent cohorts.

Carbendazim: disposition, cellular permeability, metabolite identification, and pharmacokinetic comparison with its nanoparticle.

The purpose of this study was to systematically evaluate the pharmacokinetic profiles of carbendazim, a novel anticancer drug. Carbendazim reached the highest concentrations in stomach and small intestine by 1 h after oral administration (500 mg/kg) to tumor-bearing nude mice. Four hours later, carbendazim in the large intestine reached maximum concentrations, probably because of pH-induced precipitation of the drug in the large intestine.

Effect of nanonization on absorption of 301029: ex vivo and in vivo pharmacokinetic correlations determined by liquid chromatography/mass spectrometry.

Purpose: To compare Caco-2 monolayer permeability and in vivo bioavailability of microparticle with nanoparticle 301029, a thiadiazole derivative, and to determine whether nanonization could improve oral bioavailability of the poorly soluble compound.

Methods: The mean particle size of 301029 was reduced from 7 microm to 280 nm by pearl milling. In the ex vivo assay, both microparticle and nanoparticle 301029 at the same concentration were separately added to apical side and were collected from basolateral side of Caco-2 monolayer.

Pharmacokinetic comparison of intravenous carbendazim and remote loaded carbendazim liposomes in nude mice.

Carbendazim is a novel anticancer agent. The aim of this study was to prepare and characterize a remote loaded liposome preparation of carbendazim, and compare its pharmacokinetic profile to that of unencapsulated carbendazim. Carbendazim was encapsulated in liposomes composed of sphingomyelin-cholesterol (3:1, w/w) by remote loading in response to a transmembrane pH gradient (pH 0.