By Arnold M. Friedman
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Duche´, J. ; Tillement, J. P. Br. J. Clin. Pharmacol. 1993, 36, 241–249. 7. Tillement, J. ; Se´bille, B. Adv. Drug Res. 1984, 13, 60–90. 8. ; Tillement, J. ; Barre´, J. ; VHCA: Zurich, Switzerland, 2001, pp 189–215. 9. Brodie, B. ; Schanker, L. J. J. Pharmacol. Exp. Ther. 1980, 130, 20–25. 10. ; Bechtel, Y. , Tillement, J. ; Clinical Medicine Series; McGraw-Hill: London, UK, 2000, pp 25–36. 11. ; Perrier, D. ; Dekker: New York, 1982. 12. ; Tozer, T. N. ; Williams & Wilkins: Baltimore, MD, 1995.
As compounds are increasingly optimized for metabolic stability, extrahepatic metabolic routes and direct excretion of unchanged drug 33 34 In Vivo Absorption, Distribution, Metabolism, and Excretion Studies in Discovery and Development molecules are often seen, requiring in vivo studies in animals and man. The completeness of excretion, the excretory pathways, and the metabolite patterns in plasma and excreta are studied sequentially in the animal species involved in toxicity studies and finally in man using radiolabeled drugs.
4. ICH Topic S3A, Step 5 Note for Guidance on Toxicokinetics: A Guidance for Assessing Systemic Exposure in Toxicology Studies (CPMP/ ICH384/95 – adopted November 1994). org (accessed April 2006). 5. ; Urien, S. Distribution of Drugs. , Tillement, J. ; Clinical Medicine Series McGraw-Hill: London, UK, 2000, pp 37–43. 6. ; Duche´, J. ; Tillement, J. P. Br. J. Clin. Pharmacol. 1993, 36, 241–249. 7. Tillement, J. ; Se´bille, B. Adv. Drug Res. 1984, 13, 60–90. 8. ; Tillement, J. ; Barre´, J. ; VHCA: Zurich, Switzerland, 2001, pp 189–215.
Actinides in the Environment by Arnold M. Friedman