Purpose: These two studies investigated the safety and efficacy of subcutaneous (SC) methylnaltrexone to treat opioid-induced constipation (OIC) in patients with advanced illness (AI). Constipation is a common and distressing side effect of opioid treatment. Patients (pts) with AI often experience severe OIC, which is debilitating and complicates pain management. Methylnaltrexone, a quaternary derivative of the opioid antagonist naltrexone, antagonizes the peripheral effects of opioids without effecting analgesia and does not cross the blood brain barrier.^1,2 Methods: Study 301 enrolled 154 pts who were given a single dose of methylnaltrexone 0.15 or 0.30mg/kg, or placebo. In the 302 study, 133 pts received either placebo or methylnaltrexone 0.15mg/kg SC QOD for 2 weeks. Pts had a life expectancy of <6 months, no laxation for 48 hours, and were on opioids and stable doses of laxatives. The primary efficacy endpoint was laxation within 4 hours after a first dose of study drug. Additional endpoints were laxation within 24 hours, laxation occurring within 4 hours of at least 2 of first 4 doses (302 study), adverse events (AE), pain scores, and opioid withdrawal symptoms. Results: Methylnaltrexone-treated pts had improved laxation (62% in 301 study and 48.4% in 302 study) within the first 4 hours of study drug administration. Medain time to laxation was significantly (p<0.0001) greater for the 0.15mg/kg dose (70 min) and 0.30 mg/kg dose (45 min) compared with placebo (>24 hrs). No significant changes in pain scores were noted. There were no reports of systemic opioid withdrawal due to study medication. In both studies, methylnaltrexone was well tolerated with transient abdominal cramping and flatulence being the most common AEs. Conclusions: SC methylnaltrexone effectively induces laxation in AI pts with OIC upon single and QOD dosing. The drug acts quickly, and is generally well tolerated.