Effects of cysteine on the pharmacokinetics of docetaxel in rats with protein-calorie malnutrition
| Autor: | Young Hee Choi, Insoo Yoon, Yoon Gyoon Kim, Myung Gull Lee |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
Time Factors Duodenum Health Toxicology and Mutagenesis Administration Oral Docetaxel Toxicology Kidney Weight Gain Biochemistry Protein-Energy Malnutrition Rats Sprague-Dawley Animals Humans Rhodamine 123 Cysteine Pharmacology Dose-Response Relationship Drug Biological Transport General Medicine Blood Proteins Organ Size Rats Kinetics Liver Injections Intravenous Microsomes Liver Taxoids Caco-2 Cells Energy Intake Blood Chemical Analysis Protein Binding |
| Zdroj: | Xenobiotica; the fate of foreign compounds in biological systems. 42(5) |
| ISSN: | 1366-5928 |
| Popis: | The objective of this study is to report the effects of cysteine on the pharmacokinetics of intravenous and oral docetaxel in rats with protein-calorie malnutrition (PCM). The in vivo pharmacokinetics and in vitro hepatic/intestinal metabolism of docetaxel were assessed using control, CC (control with cysteine), PCM and PCMC (PCM with cysteine) rats. The effects of cysteine on the intestinal absorption of docetaxel were further investigated through in vitro transport studies using rat intestine and Caco-2 cell monolayers. The AUCs (the areas under the plasma concentration-time curve from time zero to time infinity) of intravenous docetaxel in PCM rats were significantly greater than in the control rats because of the significant decrease in the hepatic CYP3A. In PCMC rats, the elevated AUCs in PCM rats returned to control levels. The AUC(0-6 h)s of oral docetaxel in PCM rats were significantly smaller than that in the control rats, mainly due to the decrease in gastrointestinal absorption. In CC and PCMC rats, oral cysteine supplement enhanced the gastrointestinal absorption of docetaxel probably via intestinal P-gp inhibition. If the present rat data could be expressed to humans, the alterations in docetaxel absorption and metabolism should be considered in designing a dosage regimen for cancer patients with PCM state after cysteine supplement. |
| Databáze: | OpenAIRE |
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