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Can anyone point me to literature discussing the clinical pharmacokinetics of oral agents (preferably oral anti-cancer agents such as erlotinib, gefitinib, or lapatinib) in patients with gastric cancer? Physiologically, these patients might have issues with gastric emptying and/or elevated pH impacting dissolution of certain dosage forms. This might be the case more so for resected or full gastrectomy patients. This is in theory; I want to see if there is an actual impact on clinical PK. I've found some literature discussing capecitabine, but given the complexities surrounding its PK and small numbers of patients, it's hard to determine the effect of gastric cancer vis-a-vis PK. Any help is appreciated.
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There is a need to select drugs for gastric cancer patients and instruct the patients with gastrectomy regarding the dosage and administration taking into consideration the individual pharmacokinetic profile of each drug in the gastrectomized patients.
Kindly find below some literature references of clinical pharmacokinetics of oral agents in gastric cancer and gastrectomized patients.
M.Fujimoto. Pharmacokinetics of cefcapene pivoxil and AS-924 in gastrectomized patients
International Journal of Antimicrobial Agents, Volume 18, Issue 5, Pages 489-494.
Makil O et al. Pharmacokinetics of ranitidine after partial gastrectomy in dogs, Journal of Pharmaceutical Sciences, Volume 80 Issue 11, Pages 1034 - 1036.
Fujimoto M. Pharmacokinetics of cefcapene pivoxil and AS-924 in gastrectomized patients. International Journal of Antimicrobial Agents, Volume 18, Issue 5, November 2001, Pages 489-494.
Kochi M et al. Effect of gastrectomy on the pharmacokinetics of S-1, an oral fluoropyrimidine, in resectable gastric cancer patients, Cancer Chemother Pharmacol. 2007 Oct;60(5):693-701.
Tsuruoka Y et al. Effect of gastrectomy on the pharmacokinetics of 5-fluorouracil and gimeracil after oral administration of S-1, Anticancer Drugs. 2006 Apr;17(4):393-9.
Maehara Y et al. Effect of gastrectomy on the pharmacokinetics of tegafur, uracil, and 5-fluorouracil after oral administration of a 14 tegafur and uracil combination, Volume 33, Number 6 / November, 1994.
Yamamoto Y et al. The effect of gastrectomy on serum 5-FU concentrations of patients administered UFT per os. Jpn J Cancer Clin 33: 377.
Anttila MIet al. Pharmacokinetics of futrafur after intravenous and oral administration. Cancer Chemother Pharmacol 1983 10: 150.
A Pharmacokinetic Study of Capecitabine After Total Gastrectomy for Stomach Adenocarcinoma have been initiated by Cambridge University Hospitals NHS Foundation Trust.
Thanks & Regards,
Clinical Pharmacologist & Principal Investigator,
Azidus Research Laboratories, Chennai.
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