Disposition of 3H-selamectin and 3H-ivermectin in the brain of the cat flea Ctenocephalides felis felis using micro-image analysis.
In addition to intrinsic potency and metabolic stability, the disposition of an antiparasitic drug within the target parasite plays a major role in determining drug activity. A novel technique that allows the disposition of radiolabelled drugs to be visualised within the body of the cat flea (Ctenocephalides felis felis) is described. The concentrations of two macrocyclic lactones, (3)H-selamectin and (3)H-ivermectin, within the supra- and sub-oesophageal ganglia of the flea brain following in vitro feeding of fleas on different doses of drug solubilised in calf blood have been measured. Drug disposition was visualised in cryostat sections of fleas using a micro-image analysis (MIA). A relationship between the concentration of radioactivity in the ganglia and the dose of drug in the blood meal was obtained. The concentration of selamectin in the ganglia was significantly higher than ivermectin at all doses investigated. The enhanced concentration of selamectin, at a site rich in glutamate-gated chloride channels may, in part, explain the higher potency of selamectin against fleas compared to ivermectin.
Phipps
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AN
Department of Veterinary Medicine Discovery, Pfizer Animal Health, Sandwich, Kent CT13 9NJ, UK.
Martin-Short
M R
MR
Littlewood
L
L
Blanchflower
S E
SE
Gration
K A F
KA
D000818:Animals; D000977:Antiparasitic Agents / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D010574:Pesticide Synergists / Q000494:pharmacology; D010882:Piperonyl Butoxide / Q000494:pharmacology; D011877:Radionuclide Imaging; D005423:Siphonaptera / Q000378:metabolism*; D014316:Tritium
D000977:Antiparasitic Agents; D010574:Pesticide Synergists; D014316:Tritium; D007559:Ivermectin; C414354:selamectin; D010882:Piperonyl Butoxide