Pharmacokinetic study of infusional valspodar

Margaret K. Ma, Howard L. McLeod, Peter Westervelt, Paula M. Fracasso

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


The pharmacokinetics of valspodar (PSC 833), a selective second-generation P-glycoprotein modulator, was evaluated as part of a Phase I study to modulate paclitaxel therapy in 15 patients with refractory malignancies. Valspodar was given intravenously at 1.42 mg/kg/h for 2 hours, followed by a 27-hour continuous infusion at 0.42 mg/kg/h. Serial blood samples were obtained after intravenous infusion of valspodar and paclitaxel. Valspodar disposition was best described by a linear two-compartment model. The median (range) valspodar clearance was 0.40 ml/min/kg (0.07-1.40 ml/min/kg). The 20-fold interpatient variability in valspodar clearance was not correlated with age, body weight, or gender but might be associated with coadministered medications that were metabolized via cytochrome P450 3A-mediated elimination. Valspodar whole-blood concentrations were maintained above the target threshold of 1000 ng/ml for a median of 32 hours. The pharmacokinetic model generated from this study allows for application in future studies to optimize the use of valspodar.

Original languageEnglish
Pages (from-to)412-418
Number of pages7
JournalJournal of clinical pharmacology
Issue number4
StatePublished - 2002


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