The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Phase I pharmacokinetics study of high-dose fotemustine and its metabolite 2-chloroethanol in patients with high-grade gliomas.

The pharmacokinetics of high-dose fotemustine followed by autologous bone-marrow transplantation during a phase I-II clinical trial in 24 patients with glioblastoma or astrocytoma (grade III-IV) was investigated. Plasma levels of fotemustine were determined by high-performance liquid chromatography (HPLC) and UV detection. The metabolite, 2-chloroethanol, was simultaneously followed in six patients by gag liquid chromatography and electron capture detection (GLC-ECD) assay. The drug was given as a 1-h infusion on 2 consecutive days. In all, 40 pharmacokinetic determinations of fotemustine were made at dose levels ranging from 2 x 300 to 2 x 500 mg/m2. Plasma drug elimination was best described by a bi-exponential model, with short distribution and elimination half-lives of 4.15 +/- 2.57 and 28.8 +/- 12.1 min being observed, respectively. No significant difference in half-lives or clearance was seen between the first and the second administration. During dose escalation, the mean area under the concentrationtime curve (AUC) increased from 5.96 +/- 2.89 to 12.22 +/- 3.95 mg l-1 h. Drug clearance was independent of the dose given and equal to 109 +/- 65 l/h, indicating no possible saturation of metabolism and elimination mechanisms at these high-dose levels. The metabolite 2-chloroethanol appeared very early in plasma samples. Its elimination was rapid and rate-limited by the kinetics of the parent compound, giving the same apparent terminal half-life. A close relationship between AUC and C45 values was evidenced (r = 0.890). Associated with the stability of fotemustine kinetic parameters, this could be used in future studies for individual dose adjustment, particularly for high-dose fractionated regimens.[1]

References

  1. Phase I pharmacokinetics study of high-dose fotemustine and its metabolite 2-chloroethanol in patients with high-grade gliomas. Tranchand, B., Lucas, C., Biron, P., Giroux, B., Gordon, B., Richards, R., Solere, P., Roux, N., Evene, E., Mornex, F. Cancer Chemother. Pharmacol. (1993) [Pubmed]
 
WikiGenes - Universities