Validation of a limited sampling model to determine etoposide area under the curve.

Study Objective: To validate the utility of a previously reported 3-point limited sampling model (LSM) for determining etoposide area under the curve to infinity (AUC(infinity)).

Design: Secondary analysis of data from two clinical trials of etoposide.

Setting: University medical center clinical research center.

Interaction of cyclosporin derivatives with the ATPase activity of human P-glycoprotein.

1. P-glycoprotein, a 170-180 kDa membrane glycoprotein that mediates multidrug resistance, hydrolyses ATP to efflux a broad spectrum of hydrophobic agents. In this study, we analysed the effects of three MDR reversing agents, verapamil, cyclosporin A and [3'-keto-Bmt1]-[Val2]-cyclosporin (PSC 833), on the adenosine triphosphatase (ATPase) activity of human P-glycoprotein.

Description of blood pressure changes in patients beginning cyclosporin A therapy.

Cyclosporin A (CyA) is the primary immunosuppressive agent for the prophylaxis of rejection episodes in renal, cardiac, liver, and other transplants. Recently, its use in autoimmune diseases has been investigated as well. Although several studies have produced promising results, nephrotoxicity and hypertension can result from CyA treatment, and their development must be understood in order to facilitate patient management.

Reversal of multidrug resistance by SDZ PSC 833, combined with VAD (vincristine, doxorubicin, dexamethasone) in refractory multiple myeloma. A phase I study.

SDZ PSC 833, a non-immunosuppressive cyclosporin analogue reverses multidrug resistance (MDR) in vitro by inhibiting P-glycoprotein (P-gp) mediated drug efflux. We performed a dose escalation study of SDZ PSC 833 combined with VAD chemotherapy in refractory multiple myeloma (MM). Twenty-two MM patients who were refractory to doxorubicin/vincristine/dexamethasone (VADr, n=11) or had failed multiple regimens (n=6) or were melphalan-refractory (MELr, n=5), were treated with one to three cycles of VAD combined with oral SDZ PSC 833, which was administered at escalating dosages starting at 5 mg/kg/day to 15 mg/kg/day for 7 days.