HPLC method for monitoring SDZ PSC 833 in whole blood

P-glycoprotein (Pgp) is a 170-kDa membrane transporter that mediates drug efflux and is an effector of multidrug resistance. SDZ PSC 833 (PSC), a nonimmunosuppressive cyclosporine that potently modulates Pgp, is currently under clinical evaluation in patients with cancer. We have developed a reverse...

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Bibliographic Details
Published in:Clinical chemistry (Baltimore, Md.) Md.), 1997-03, Vol.43 (3), p.505-510
Main Authors: Scott, Mitchell G, Hock, Karl G, Crimmins, Daniel L, Fracasso, Paula M
Format: Article
Language:English
Subjects:
Analysis
Antineoplastic Agents, Phytogenic - administration & dosage
Biological and medical sciences
Chromatography, High Pressure Liquid - methods
Cross Reactions
Cyclosporine - blood
Cyclosporins - blood
Cyclosporins - therapeutic use
Drug Monitoring - methods
Fluorescence Polarization Immunoassay
General pharmacology
Humans
Immunosuppressive Agents - blood
Immunosuppressive Agents - therapeutic use
Medical sciences
Neoplasms - blood
Neoplasms - drug therapy
Paclitaxel - administration & dosage
Pharmacology. Drug treatments
Reproducibility of Results
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Summary:P-glycoprotein (Pgp) is a 170-kDa membrane transporter that mediates drug efflux and is an effector of multidrug resistance. SDZ PSC 833 (PSC), a nonimmunosuppressive cyclosporine that potently modulates Pgp, is currently under clinical evaluation in patients with cancer. We have developed a reversed-phase HPLC assay for determining PSC blood concentrations that utilizes a step gradient with linear segments to resolve PSC into two distinct peaks (likely to be keto and enol isomers). To clinically validate the assay, PSC concentrations were obtained by HPLC from nine patients receiving oral doses of 5 mg/kg every 6 h. Values ranged from 0.91 to 5.4 mg/L during the dosing period, comparable with concentrations of PSC that modulate Pgp in vitro. In addition, we investigated the immunoreactivity of the Abbott TDx cyclosporin A (CsA) monoclonal whole-blood assay for PSC. The TDx CsA assay cross-reacts approximately 17% with PSC as determined by adding known amounts of PSC to whole blood. When PSC concentrations obtained by the TDx CsA assay were divided by 0.17, we found agreement between the TDx CsA assay and the HPLC PSC assay for samples from nine patients.
ISSN:0009-9147
1530-8561
DOI:10.1093/clinchem/43.3.505