Scutellaria baicalensis decreases ritonavir-induced nausea

BACKGROUND: Protease inhibitors, particularly ritonavir, causes significant gastrointestinal disturbances such as nausea, even at low doses. This ritonavir-induced nausea could be related to its oxidative stress in the gut. Alleviation of drug-induced nausea is important in effectively increasing patients' compliance and improving their quality of life. Conventional anti-emetic drugs can only partially abate the symptoms in these patients, and their cost has also been a concern. Rats respond to nausea-producing emetic stimuli by increasing consumption of non-nutritive substances like kaolin or clay, a phenomenon known as pica. In this study, we used this rat pica model to evaluate the effects of Scutellaria baicalensis, a commonly used oriental herbal medicine, on ritonavir-induced nausea. RESULTS: Rats treated with 20 mg/kg ritonavir significant caused increases of kaolin consumption at 24 to 48 hr (P < 0.01). Pretreatment with 0.3 and 3 mg/kg Scutellaria baicalensis extract significantly decreased ritonavir-induced kaolin intake in a dose-related manner (P < 0.01). Compared to vehicle treatment, the extract completely prevented ritonavir-induced kaolin consumption at dose 3 mg/kg. The area under the curves (AUC) for kaolin intake from time 0 to 120 hr for vehicle only, ritonavir only, SbE 0.3 mg/kg plus ritonavir, and SbE 3 mg/kg plus ritonavir were 27.3 g•hr, 146.7 g•hr, 123.2 g•hr, and 32.7 g•hr, respectively. The reduction in area under the curves of kaolin intake from time 0 to 120 hr between ritonavir only and SbE 0.3 mg/kg plus ritonavir, ritonavir only and SbE 3 mg/kg plus ritonavir were 16.0% and 77.7%, respectively. CONCLUSION: Scutellaria baicalensis significantly attenuated ritonavir-induced pica, and demonstrated a potential in treating ritonavir-induced nausea

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

<p>Abstract</p> <p>Background</p> <p>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 <it>mu</it>-opioid receptor antagonist that does not affect analgesia, on ritonavir-induced nausea and vomiting in a rat pica model.</p> <p>Results</p> <p>We observed that 24 to 48 hr after administration of oral ritonavir 20 mg/kg, kaolin consumption increased significantly in rats (<it>P </it>< 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 (<it>P </it>< 0.01) and also with naloxone (0.1–0.3 mg/kg) (<it>P </it>< 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.</p> <p>Conclusion</p> <p>These results suggest that methylnaltrexone may have potential clinical utility in reducing nausea and vomiting in HIV patients who take ritonavir.</p