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AIDS Research and Therapy 2009-Aug

Protease inhibitor-induced nausea and vomiting is attenuated by a peripherally acting, opioid-receptor antagonist in a rat model.

Vain rekisteröityneet käyttäjät voivat kääntää artikkeleita
Kirjaudu sisään Rekisteröidy
Linkki tallennetaan leikepöydälle
Chun-Su Yuan
Chong-Zhi Wang
Sangeeta R Mehendale
Han H Aung
Adela Foo
Robert J Israel

Avainsanat

Abstrakti

BACKGROUND

Protease inhibitors such as ritonavir can cause nausea and vomiting which is the most common reason for discontinuation. Rats react to nauseous and emetic stimuli by increasing their oral intake of non-nutritive substances like kaolin, known as pica behavior. In this study, we evaluated the effects of methylnaltrexone, a peripherally acting mu-opioid receptor antagonist that does not affect analgesia, on ritonavir-induced nausea and vomiting in a rat pica model.

RESULTS

We observed that 24 to 48 hr after administration of oral ritonavir 20 mg/kg, kaolin consumption increased significantly in rats (P < 0.01). This increase was attenuated by pretreatment with an intraperitoneal injection of methylnaltrexone (0.3-3.0 mg/kg) in a dose dependent manner (P < 0.01) and also with naloxone (0.1-0.3 mg/kg) (P < 0.01). The areas under the curve for kaolin intake from time 0 to 120 hr were significantly reduced after administration of the opioid antagonists. Food intake was not significantly affected. Plasma naltrexone levels were measured after methylnaltrexone injection, and no detectable levels were found, indicating that methylnaltrexone was not demethylated in our experimental paradigm.

CONCLUSIONS

These results suggest that methylnaltrexone may have potential clinical utility in reducing nausea and vomiting in HIV patients who take ritonavir.

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