Abstract
BackgroundProtease 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.ResultsWe 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.ConclusionThese results suggest that methylnaltrexone may have potential clinical utility in reducing nausea and vomiting in HIV patients who take ritonavir.
Highlights
Infection with the human immunodeficiency virus (HIV), which may progress to acquired immune deficiency syndrome (AIDS), is a deadly disease that affects many millions of people worldwide [1,2]
We evaluated the effects of methylnaltrexone on ritonavir-induced nausea and vomiting in the rat pica model
At 30 mg/kg, kaolin intake did not increase further, and the ritonavir dose used for this study was 20 mg/kg
Summary
Infection with the human immunodeficiency virus (HIV), which may progress to acquired immune deficiency syndrome (AIDS), is a deadly disease that affects many millions of people worldwide [1,2]. If patients are not treated in a timely fashion, the disease can cause morbidity and lead to death because of immune dysfunction and opportunistic infections. Adverse effects deteriorate quality of life, but negatively affect compliance [5]. Nausea and vomiting are examples of drug-induced adverse effects that may affect compliance [4,6,7]. Protease inhibitors such as ritonavir can cause nausea and vomiting which is the most common reason for discontinuation. 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
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