The purpose of this study is to examine the safety and activity of MNTX in relieving opioid-induced constipation following orthopedic procedures.

This is a double-blind, randomized, parallel-group, placebo- controlled Phase 2 study to evaluate the safety and activity of subcutaneous (SC) MNTX versus SC placebo in participants who have undergone orthopedic procedures and who are expected to require opioids for 1 week after randomization. Participants will sign an informed consent form and be screened between Days 4-10 after their orthopedic procedure. Those participants who meet all eligibility requirements will be enrolled in the study. Treatment with study medication will be continued until either the participant no longer requires opioid medication for pain relief or the maximum number of doses is reached. Originally, participants were receiving treatment for up to 7 days. Then after Protocol Amendment 1 (12 March 2008), the duration of treatment changed from "up to 7 days" to "up to 4 days".

Inclusion Criteria:

1. Male and female participants greater than or equal to (>=) 18 years of age.
2. Participants must have undergone an orthopedic procedure (that is, total knee or hip replacement, spinal fusion, or reduction of fracture(s) with or without surgical fixation post trauma).
3. Participants must be receiving opioid analgesics (a mu agonist only-not to include agents with mixed mechanisms of action such as tramadol or buprenorphine) after the procedures and be expected to require daily opioid analgesics for at least 7 days post randomization.
4. Participants must be acutely constipated following their orthopedic procedure.
5. Participants must receive all doses of study drug in either hospitals or rehabilitation facilities.
6. Participants must sign an informed consent form.
7. Females of childbearing potential must have a negative pregnancy test and use appropriate birth control throughout the study.
8. Body weight within range of 40 kilograms (kg) - 150 kg (88 - 330 pounds [lbs]).

Exclusion Criteria:

1. Participants with known hypersensitivity to methylnaltrexone, naltrexone, or naloxone.
2. Participants who received any investigational new drug (experimental) in the previous 30 days.
3. Participants who have received a laxative (for example, lactulose) or an enema within 48 hours prior to the first dose.
4. Participants with constipation not attributed to post procedure opioids.
5. Participants with a history of alcohol or prescription or non-prescription drug abuse within the past 2 years.
6. Female participants who are pregnant or lactating.
7. Participants with a known history of chronic active hepatitis B or hepatitis C virus or human immunodeficiency virus (HIV) infection.