The pharmacology of indomethacin, a prostaglandin biosynthesis inhibitor, in larvae of the tobacco hornworm, Manduca sexta

Abstract

We describe the uptake, metabolism and elimination of the prostaglandin biosynthesis inhibitor, indomethacin, by an insect. Radioactive indomethacin was injected into the hemocoels of tobacco hornworms, Manduca sexta, and the movement of the compound within their bodies was monitored. Indomethacin rapidly moved from hemolymph circulation into all major tissues, and was slowly metabolized within tissues. Over 90% of the radioactive indomethacin was cleared from the hemolymph in less than 10 min after injection. Less than half of the indomethacin was removed from the tissues during the first 24h after injection. Further, the indomethacin appeared to be metabolized into polar products after it came into contact with the frass. Because the compound is quickly taken into tissues and remains unmetabolized within the tissues for physiologically relevant periods of time, we propose that indomethacin is an appropriate probe to use in studies of the physiological actions of eicosanoids in insects and other invertebrates.