Inactive renal elimination
sufficiently lipophilic to cross the blood-brain barrier, yet it displays no CNS-opioid effects. The reason for this is that it is actively pumped out of the brain via the P-glycoprotein pump (MDR1).87 Knockout mice with the P-glycoprotein pump genetically removed were given radiolabeled loperamide and sacrificed 4 hours later. The [3H]loperamide concentrations were measured and compared with wild-type mice. A 13.5-fold increase in loperamide concentration was found in the brain of the knockouts. In addition, the mice lacking the P-glycoprotein pump displayed pronounced signs of central opiate agonism.87 Loperamide is available as 2-mg capsules for treatment of acute and chronic diarrhea. Recommended dosage is 4 mg initially, with 2 mg after each loose stool for a maximum of 16 mg/d.
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