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)
 
 
 
 
 

A phase I clinical pharmacologic study of pralatrexate in combination with probenecid in adults with advanced solid tumors.

PURPOSE: The antifolate pralatrexate (10-propargyl-10-deazaaminopterin, PDX) demonstrates greater in vitro and in vivo antitumor efficacy than methotrexate. Preclinical models indicated that the efficacy of pralatrexate may be enhanced by coadministration with probenecid. The aim of this phase I study was to determine the maximum-tolerated dose of pralatrexate when combined with probenecid given every 2 weeks in humans. METHODS: The starting dose was pralatrexate 40 mg/m(2) intravenously and probenecid 70 mg/m(2) intravenously administered every 14 days, where one cycle of treatment was every 28 days. The pralatrexate dose was initially fixed while probenecid dose escalation was explored. The pralatrexate area under the curve (AUC), terminal-half life (t1/2), and maximum plasma concentration (Cmax) were determined in cycle 1. RESULTS: Seventeen patients with advanced solid tumors were treated with a median of two prior chemotherapy regimens. Stomatitis was dose-limiting with pralatrexate 40 mg/m(2) and probenecid 233 mg/m(2). Mean pralatrexate AUC and half life (t1/2) increased with increasing doses of probenecid. No objective responses were seen. CONCLUSION: For patients with advanced solid tumors, the maximum-tolerated dose of this drug combination was pralatrexate 40 mg/m(2) and probenecid 140 mg/m(2). Vitamin B(12) and folate supplementation may allow for further dose escalation of pralatrexate and probenecid. This is a suitable question for a future study.[1]

References

  1. A phase I clinical pharmacologic study of pralatrexate in combination with probenecid in adults with advanced solid tumors. Fury, M.G., Krug, L.M., Azzoli, C.G., Sharma, S., Kemeny, N., Wu, N., Kris, M.G., Rizvi, N.A. Cancer Chemother. Pharmacol. (2006) [Pubmed]
 
WikiGenes - Universities