Advisory Committee for Pharmaceutical Science

November 3-4, 2004



Day 1: Wednesday, November 3, 2004


Topic 1        Pharmacogenetics of Irinotecan:  Scientific and Clinical Impact of UGT Polymorphism


  1. Background information


2.    Beutler E et al.  Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: A balanced polymorphism for regulation of bilirubin metabolism? Proc. Natl. Acad. Sci 1998; 95:8170-8174.


  1. Innocenti F et al. Genetic variants in the UDP-glucuronasyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 2004; 22(8); 1382-1388.


  1. Rouits E et al. Relevance of different UGT1A1 polymorphisms in irinotecan-induced toxicity: a molecular and clinical study of 75 patients.  Clin Cancer Res 2004; 10:5151-5159.


  1. Marcuello E et al. UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer. British J Cancer 2004; 91:678-682.


  1. Iyer L et al.  UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity.  Pharmacogenomics J 2002; 2:43-47.


  1. Ando Y et al.  Polymorphisms of UDP-glucuronosyl-transferase gene and irinotecan toxicity: A pharmacogenetic analysis. Cancer Res. 2000; 60:6921-6926.



Topic 2:       Drug-Drug Interaction Concept Paper: Issues Related to Transporter- and Induction-Based Interactions and Multiple Inhibitor Drug Interaction Studies


  1. Concept paper” Drug interaction studies- Study Design, Data Analysis, and Implications for Dosing and Labeling


  1. Tucker G, Houston JB, and Huang S-M, Optimizing drug development: strategies to assess drug metabolism/transporter interaction potential- toward a consensus, Clin Pharmacol Ther. 2001 Aug;70(2):103-14; Br J Clin Pharmacol. 2001 Jul;52(1):107-17; , Eur J Pharm Sci. 2001 Jul;13(4):417-28; Pharm Res. 2001 Aug;18(8):1071-80.


  1. Bjorrnsson TD, Callaghan JT,  Einolf HJ, Fischer V, Gan L, Grimm S, et al, The Conduct Of In Vitro And In Vivo Drug-Drug Interaction Studies: A Pharmaceutical Research and Manufacturers of America (Phrma) Perspective, Drug Metab Disp 31: 815-832, 2003


  1. Huang, S-M, Hall, SD, Watkins, P, Love, LA, Serabjit-Singh, C, Betz, et al, Drug Interactions with Herbal Products & Grapefruit Juice:  A Conference Report, Clin Pharmacol Ther 2004 Jan;75(1):1-12


  1. Huang, S-M, Lesko, LJ, Drug-drug, drug-dietary supplement and drug-citrus fruit and other food interactions- what have we learned? J Clin Pharmacol 2004 Jun;44(6):559-69



Day 2: Thursday, November 4, 2004


Topic 3          Transition of Biomarkers to Surrogate Endpoints: A New Critical Path Initiative


  1. Lesko LJ, Atkinson, AJ, Use Of Biomarkers And Surrogate Endpoints In Drug Development and Regulatory Decision Making, Annu. Rev. Pharmacol. Toxicol. 2001. 41:347–66


  1. “Challenge and Opportunity on the Critical Path to New Medical Products". FDA white paper available on the FDA Website: