Effects of cysteine on the pharmacokinetics of tamoxifen in rats with protein-calorie malnutrition

Yu Kyung Lee, Insoo Yoon, Myung Gull Lee, Young Hee Choi

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Protein-calorie malnutrition (PCM) could occur frequently in cancer patients and alter the pharmacokinetics of drugs. Also cysteine shows anti-oxidative effect and changes the activities of drug metabolizing enzyme and/or transporters. Herein, we investigated the effects of cysteine on the pharmacokinetics of tamoxifen in rats with protein-calorie malnutrition (PCM). The in vivo pharmacokinetics and in vitro hepatic/intestinal metabolism of tamoxifen were assessed using control, CC (control with cysteine), PCM, PCMC (PCM with cysteine) rats. The effects of cysteine on the intestinal absorption of tamoxifen were further investigated through in vitro transport studies using rat intestine. The AUCs of intravenous tamoxifen in PCM rats were significantly greater than control rats due to the decrease in the hepatic metabolism via CYP3A. In PCMC rats, the elevated AUCs in PCM rats returned to control levels by oral cysteine supplement. The AUC of oral tamoxifen in PCM rats was significantly smaller than in control rats mainly due to the decrease in gastrointestinal absorption. In CC and PCMC rats, oral cysteine supplement enhanced the gastrointestinal absorption of tamoxifen probably via intestinal P-gp inhibition. The present study demonstrated that PCM state and/or oral cysteine supplement had a profound impact on the pharmacokinetics of tamoxifen in rats. If the present rat data are extrapolated to humans, the alterations in tamoxifen absorption and metabolism should be considered in designing a dosage regimen for cancer patients with PCM and/or oral cysteine supplement.

Original languageEnglish
Pages (from-to)1225-1234
Number of pages10
JournalXenobiotica
Volume42
Issue number12
DOIs
StatePublished - Dec 2012

Keywords

  • Cysteine
  • Cytochrome P450
  • P-glycoprotein
  • Pharmacokinetics
  • Protein-calorie malnutrition
  • Rats
  • Tamoxifen

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