title: Excretion and biotransformation of alfentanil and sufentanil in rats and dogs.
abstract: The excretion and biotransformation of alfentanil (ALF) and sufentanil (SUF), two recent analogues of the synthetic opioid fentanyl, were studied after single iv administration of the tritium-labeled drugs in male rats and dogs. The drugs were almost completely metabolized in the two species, which resulted in a large number of metabolites. The excretion of the metabolites was rapid and exceeded 95% within 4 days, except for that of ALF metabolites in dogs (about 85%). For ALF, excretion of the radioactivity with the urine (73% in rats, about 76% in dogs) exceeded that with the feces. For SUF, excretion of the radioactivity with the urine amounted to 38 and 60% and that with the feces to 62 and 40%, in rats and dogs, respectively. Bile-cannulated rats excreted 68% with the bile within 24 hr after SUF dosing, and about 22% of this biliary radioactivity was subjected to enterohepatic circulation. After an ALF dose, the biliary excretion amounted to 24%, and the enterohepatic circulation was minimal. The main metabolic pathways of the two drugs were the oxidative N-dealkylation at the piperidine nitrogen and at the amide nitrogen, oxidative O-demethylation, aromatic hydroxylation, and the formation of ether glucuronides. N-[4-(Hydroxymethyl)-4-piperidinyl]-N-phenylpropanamide (M6) was the main metabolite of both ALF and SUF in rats. In dogs, the glucuronide of N-(4-hydroxyphenyl)propanamide (M5) was the main metabolite of ALF. After SUF dosing in dogs, N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide was more abundant than M5.
mesh_terms: D015760:Alfentanil; D000777:Anesthetics / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D017409:Sufentanil
chemical_list: D000777:Anesthetics; D015760:Alfentanil; D017409:Sufentanil; D005283:Fentanyl