slide1
Download
Skip this Video
Download Presentation
Robert O. Kumi, Ph.D. Reviewer, Pharmacokinetics

Loading in 2 Seconds...

play fullscreen
1 / 13

Robert O. Kumi, Ph.D. Reviewer, Pharmacokinetics - PowerPoint PPT Presentation


  • 85 Views
  • Uploaded on

Pharmacokinetic Information Submitted to Support Valganciclovir Use in Maintenance Therapy for CMV Retinitis. Robert O. Kumi, Ph.D. Reviewer, Pharmacokinetics Food and Drug Administration, Office of Clinical Pharmacology and Biopharmaceutics, Division of Pharmaceutical Evaluation III.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Robert O. Kumi, Ph.D. Reviewer, Pharmacokinetics' - maude


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

Pharmacokinetic Information Submitted to Support Valganciclovir Use in Maintenance Therapy for CMV Retinitis

Robert O. Kumi, Ph.D.

Reviewer, Pharmacokinetics

Food and Drug Administration, Office of Clinical Pharmacology and Biopharmaceutics, Division of Pharmaceutical Evaluation III

outline valganciclovir pharmacokinetics
Outline: Valganciclovir Pharmacokinetics
  • Background
  • Studies and Analyses Conducted
  • Summary of Study Results
  • Conclusions
ganciclovir delivery systems
Ganciclovir Delivery Systems
  • Intravenous and oral ganciclovir formulations available for maintenance therapy
    • Oral capsule has poor bioavailability (F):F < 10 % in the presence of food
  • Valganciclovir hydrochloride NDA under review
valganciclovir prodrug of ganciclovir
Valganciclovir- Prodrug of Ganciclovir
  • VALGAN is rapidly and extensively converted to GCV and valine
  • Following VALGAN administration, GCV bioavailability in presence of food is approximately 60 %
  • Low Systemic Availability of VALGAN: VALGAN Exposure < 5 % of GCV Exposure
valgan use in maintenance therapy studies and analyses conducted
VALGAN Use in Maintenance Therapy: Studies and Analyses Conducted
  • Exposure-Response (PK/PD) Analysis (GANS 2226)

Applicant concluded that AUCavg was the best predictor of time to first photographic progression

  • Pharmacokinetic comparisons of GCV delivery systems
ganciclovir pk pd analysis
Ganciclovir PK/PD Analysis
  • Objective
    • to determine if any GCV PK parameter (s) predict response (time to first photographic progression) during maintenance therapy
  • Methodology
    • three oral GCV dose regimens and one IV GCV dose regimen
    • PK parameter estimates obtained using population approach
    • Population PK parameter estimates were used to evaluate PK/PD relationship
limitations of gcv pk pd analysis
Limitations of GCV PK/PD Analysis
  • Errors in PK parameter estimates anticipated due to insufficient dosing time records
  • Accuracy of individual parameter estimates unknown, because of the sampling scheme used
  • Population pharmacokinetic analysis results could not be used for further PK/PD analysis
pharmacokinetic comparisons alternative to pk pd analysis
Pharmacokinetic Comparisons: Alternative to PK/PD Analysis

Plasma concentration-time profile comparisons

  • three ganciclovir delivery systems at recommended and proposed doses
  • IV GCV, VALGAN, and Oral GCV
conclusions
Conclusions
  • GCV Plasma concentration-time profile comparisons of VALGAN to two approved GCV regimens support the use of VALGAN for CMV retinitis maintenance therapy
  • PK/PD model is not needed to support VALGAN use during maintenance therapy
acknowledgements
Acknowledgements
  • Valganciclovir Review Team
  • Sue-Chih Lee, Ph.D., Pharmacometrics Reviewer
ad