In vitro metabolism of 14C-moxidectin by hepatic microsomes from various species.
Moxidectin is an antiparasitic drug widely used in cattle, sheep and companion animals. No data were available on its metabolism in wild species or in monogastrics. The in vitro metabolism of 14C-moxidectin was studied using hepatic microsomes from several different species: cow (Bos taurus). sheep (Ovis ovis), goat (Capra hircus), deer (Cervus dama), rat (Rattus norvegicus), pig (Sus scrofa and rabbit (Oryctolagus cuniculus). After separation and quantification by HPLC, the extent of metabolism of 14C-moxidectin was greatest with microsomes from sheep (32.7%) as compared to those from cows (20.6%), deer (15.4%), goats (12.7%). rabbits (7.0%) or rats (3.0%). The least metabolism occurred with microsomes from pigs. with 0.8% of total detected metabolites. A C29 monohydroxymethyl metabolite was detected in the greatest amounts. providing 0.4% out of the total detected radioactivity in pigs and 19.3% in sheep. In addition, the importance of P450 3A in the metabolism of 14C-moxidectin was confirmed by using in vivo induced P450 in combination with various P450 inhibitors.
Dupuy
J
J
INRA-Toulouse, Laboratoire de Pharmacologie-Toxicologie, Tournefeuiille, France.
Escudero
E
E
Eeckhoutte
C
C
Sutra
J F
JF
Galtier
P
P
Alvinerie
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D000969:Antinematodal Agents / Q000378:metabolism*; D001571:Benzoflavones / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002417:Cattle; D003022:Clotrimazole / Q000494:pharmacology; D003670:Deer; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018942:Macrolides; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism*; D010574:Pesticide Synergists / Q000494:pharmacology; D010882:Piperonyl Butoxide / Q000494:pharmacology; D011817:Rabbits; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep; D013552:Swine
D000900:Anti-Bacterial Agents; D000891:Anti-Infective Agents, Local; D000969:Antinematodal Agents; D001571:Benzoflavones; D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors; D018942:Macrolides; D010574:Pesticide Synergists; C011512:alpha-naphthoflavone; D003022:Clotrimazole; D010882:Piperonyl Butoxide; C027837:moxidectin; D008797:Metyrapone