Prolonged Administration of Atropine or Histamine in a Silicone Rubber Implant

Abstract

IN the use of drugs, it is often desirable to maintain a constant blood and tissue concentration of chemical for prolonged periods. Several attempts to avoid the ‘sawtooth’ oscillations of drug-levels that accompany periodic dosing have been reported. Daily injections of histamine in a beeswax repository have been used to develop gastro-duodenal lesions in dogs1. Thompson et al.2 found that a single intramuscular injection of highly insoluble pamoate salt ((C1–501, cycloguanil pamoate) in mice and monkeys was successful as a repository drug against malaria. A constant level of medication, using silicone rubber as a carrier, was attempted by Folkman and Long3,4 for cardiac pacemaker drugs and by Powers5 in treating experimental malaria and schistosomiasis. We chose to investigate further the practicability of using silicone rubber to effect the slow release of drugs. Atropine and histamine were chosen for the study because they gave diverse but measurable responses, mydriasis in rats and gastrointestinal lesions in dogs.