An example of the use of this technology is the "retasking" of the opiate antagonist naloxol to treat opioid-induced constipation and bowel dysfunction. Opioids exert their effect by binding mu receptors in the CNS to provide analgesia. Mu receptors are also present in the gastrointestinal (GI) tract. Opioid binding in the GI tract can cause severe constipation and bowel dysfunction, which is a significant problem for patients who require continuous use of opioids to control intractable pain. It is estimated that 200 million opioid prescriptions are filled each year in the US and that more than 40% of patients will experience opioid-induced constipation and bowel dysfunction.

Figure 4: Permeation of PEG–naloxol, naloxone, and reference standards in rats. (FIGURES ARE COURTESY OF THE AUTHORS.)

Figure 5: The effect of PEG–naloxol on gastrointestinal (GI) transit time and central morphine efficacy. (FIGURES ARE COURTESY OF THE AUTHORS.)

Figure 6: Concentration of PEG–naloxol in plasma over time. (FIGURES ARE COURTESY OF THE AUTHORS.)