Pharmacokinetic and pharmacodynamic evaluation of the topoisomerase inhibitor irinotecan in cancer patients

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
E GuptaM J Ratain

Abstract

We conducted a pharmacokinetic and pharmacodynamic evaluation of irinotecan (CPT-11) and determined the effect of race and sex on disposition and toxicity of CPT-11. We tested the efficacy of acetaminophen (AAP) to phenotype SN-38 glucuronidation. Forty patients received a dose of 145 mg/m2 of CPT-11 as a 90-minute infusion. Total CPT-11, SN-38, and SN-38G were quantitated in plasma and urine samples. Following administration of 1 g AAP, urinary concentrations of AAP and AAP-glucuronide (AAP-G) were assessed. CPT-11 exhibited a mean elimination half-life (t1/2) of 8.8 hours, an average clearance (CL) of 14.6 L/h/m2, and a mean volume of distribution at steady-state (Vdss) of 136 L/m2. SN-38 and SN-38G had low plasma availabilities (3% and 10% relative to CPT-11), with mean t1/2 values of 11.6 and 10.5 hours, respectively. Urinary recovery accounted for 15% of the dose. Race and sex had no effect on the plasma availability of CPT-11, SN-38, and SN-38G. The applicability of biliary index (BI) in predicting dose-limiting intestinal toxicity was validated. Patients who developed grade 3 or 4 toxicity had significantly higher index values compared with patients with grade 0 to 2 toxicity (P = .001). There was no difference in the in...Continue Reading

Citations

May 20, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H S FriedmanL L Miller
Nov 24, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·V M HerbenW W ten Bokkel Huinink
Mar 7, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·U VanhoeferY M Rustum
Apr 6, 2001·International Journal of Cancer. Journal International Du Cancer·Y TakedaK Kudo
Sep 19, 2002·British Journal of Cancer·D OosterhoffW R Gerritsen
Oct 2, 2003·The Annals of Pharmacotherapy·Michelle A RudekWilliam D Figg
Aug 3, 2004·Journal of Clinical Pharmacology·Luca PaoluzziAlex Sparreboom
Feb 16, 2005·Expert Opinion on Drug Safety·Karen Seiter
May 17, 2005·Cancer Chemotherapy and Pharmacology·Apurva A DesaiEverett E Vokes
Apr 26, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ji-Youn HanJin Soo Lee
Jul 2, 2009·Journal of the National Cancer Institute·Otis W Brawley
Mar 9, 2010·Drug Metabolism and Pharmacokinetics·Jane P F Bai
Mar 24, 2011·The Cancer Journal·Roshawn G Watson, Howard L McLeod
Nov 26, 2015·World Journal of Gastroenterology : WJG·Ken-ichi FujitaYasutsuna Sasaki
Sep 30, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Peter J O'Dwyer, Robert B Catalano
Sep 1, 2005·Pharmaceutical Research·Quan TianShufeng Zhou
Mar 10, 2006·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Jörg T Hartmann, Hans-Peter Lipp
May 13, 2014·Asian Pacific Journal of Cancer Prevention : APJCP·Yan-Yan LuJin Xiang
Feb 25, 1998·Japanese Journal of Cancer Research : Gann·T TakahashiP I Mackenzie
Oct 26, 1999·Journal of Gastroenterology and Hepatology·B Burchell, R Hume
Jan 7, 1999·The Annals of Pharmacotherapy·R J Cersosimo
May 31, 2002·Japanese Journal of Cancer Research : Gann·Maki AndoYoshinori Hasegawa
Jul 21, 2004·Journal of Psychopharmacology·Shufeng ZhouEdmund J D Lee
Jul 20, 2007·The Journal of Pharmacology and Experimental Therapeutics·Marissa A SchielSonal P Sanghani
Mar 10, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Federico InnocentiMark J Ratain
Feb 26, 2009·Expert Opinion on Drug Metabolism & Toxicology·Sridhar ManiSanjay Goel
Aug 15, 2014·Interdisciplinary Sciences, Computational Life Sciences·Anil Kumar, Utpal Bora
Sep 28, 1998·Cancer Chemotherapy and Pharmacology·L Iyer, M J Ratain
Jan 5, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ron H J MathijssenAlex Sparreboom

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Disparities

Cancer disparities refers to differences in cancer outcomes (e.g., number of cancer cases, related health complications) across population groups.