Development of a HPLC-MS/MS assay to measure the novel proteasome inhibitor CEP-18770 in plasma. Preliminary pharmacokinetic evaluation in cancer patients

摘要

We have successfully developed a HPLC-MS/MS method to measure the novel anticancer agent CEP-18770 in plasma and to study its human pharmacokinetics during a Phase I clinical study. The dose escalation is in progress. Preliminary pharmacokinetic data, obtained on day 1 of treatment at the dose of 1.1 mg/m~(2) in 3 patients, showed a Cmax and AUCexp values (mean+-SD) of 284.0+-138.3 ng/mL and 664.7+-208.3 ng/mL*h, respectively. The drug was eliminated from plasma with a half-life of about 4 days.