Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Technology evaluation: Valspodar, Novartis AG.

H L Tai1

  • 1Roche Pharmaceuticals, Neurobiology Research, 3410 Hillview Avenue, Paulo Alto, CA 94304, USA. ezra.tai@roche.com

Current Opinion in Molecular Therapeutics
|March 16, 2001
PubMed
Summary

Valspodar (PSC-833) reverses multidrug resistance by inhibiting P-glycoprotein (P-gp). This drug shows promise in treating leukemia and ovarian cancer, with ongoing phase III trials.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Electrospray ionisation mass spectrometry: principles and clinical applications.

The Clinical biochemist. Reviews·2008
Same author

Alcoholic ketoacidosis in two Chinese patients.

Chinese medical journal·2002
Same author

Optimal treatment for distal ureteral calculi: extracorporeal shockwave lithotripsy versus ureteroscopy.

Journal of endourology·2001
Same author

Beneficial effect of intranasal desmopressin for men with benign prostatic hyperplasia and nocturia: preliminary results.

Techniques in urology·1999
Same author

Enhanced proteasomal degradation of mutant human thiopurine S-methyltransferase (TPMT) in mammalian cells: mechanism for TPMT protein deficiency inherited by TPMT*2, TPMT*3A, TPMT*3B or TPMT*3C.

Pharmacogenetics·1999
Same author

Xanthogranulomatous cystitis associated with anaerobic bacterial infection.

The Journal of urology·1999

Area of Science:

  • Pharmacology
  • Oncology
  • Drug Development

Background:

  • Valspodar (PSC-833) is a cyclosporin derivative lacking immunosuppressive and nephrotoxic effects.
  • It binds to P-glycoprotein (P-gp), reversing multidrug resistance (MDR) effectively.
  • Unlike cyclosporin A and verapamil, valspodar shows superior MDR-reversing activity in vitro and in vivo.

Purpose of the Study:

  • To evaluate valspodar's efficacy and safety as a multidrug resistance modulator.
  • To assess its potential in treating cancers like acute myeloid leukemia, multiple myeloma, and ovarian cancer.

Main Methods:

  • Preclinical and Phase I/II clinical studies were conducted.
  • Valspodar's interaction with P-glycoprotein (P-gp) and cytochrome P450 3A (CYP3A) was investigated.
  • Pharmacokinetic and toxicity profiles were assessed.

Main Results:

  • Valspodar achieves therapeutic plasma levels, inhibiting P-gp in the intestine, liver, and blood-brain barrier.
  • A new formulation improves oral bioavailability to 60% with reduced variability.
  • Acceptable toxicity, with dose-limiting cerebellar ataxia, was observed.

Conclusions:

  • Valspodar demonstrates significant multidrug resistance-modulating activity in various cancers.
  • Phase III trials are underway for acute myeloid leukemia, multiple myeloma, and ovarian cancer.
  • Valspodar represents a promising therapeutic agent for overcoming multidrug resistance in cancer treatment.

Related Experiment Videos