The metabolism of 14C-tazadolene succinate in the dog.
1. Beagle dogs dosed orally with 14C-tazadolene succinate excreted much of the dose in the urine (mean 63.1% in 5 days with most excreted in the first 24 h). A lesser proportion of the dose was excreted in the faeces (mean 20.7%) and again most of this was voided in the first 24 h. 2. Four metabolites were identified and quantified in the urine, namely 3-hydroxy-(M1), 4-hydroxy- (M2a), and 3-methoxy-4-hydroxy-tazadolene (M2b) and N-[2-(phenylmethylene)cyclohexyl]-beta-alanine (M3). 3. In the 24 h urine, M2a and b glucuronides accounted for 17.7% dose, unconjugated M2a and b for 11.3%, and M3 for 18.3%. Insufficient M1 was present to be quantified. The same metabolites were seen in the 24 h faeces, but at lower concn. Thus M2a and b glucuronides, M2a and b, and M3 were 3.2%, 4.9% and 3.5% dose respectively. 4. All three phenols were present in plasma as their glucuronides as well as the beta-alanine derivative. They all had the same tmax of 2 h and t1/2 lambda 1 of the order of 1 h.
Dring
L G
LG
Upjohn Laboratories-Europe, Upjohn Ltd, Crawley, UK.
Bye
A
A
Constable
D A
DA
Lang
J C
JC
Barsuhn
C
C
Johnston
A M
AM
D000700:Analgesics / Q000493:pharmacokinetics*; D000818:Animals; D001384:Azetidines / Q000493:pharmacokinetics*; D001711:Biotransformation; D002250:Carbon Radioisotopes; D004285:Dogs; D005965:Glucuronates / Q000378:metabolism; D008297:Male
D000700:Analgesics; D001384:Azetidines; D002250:Carbon Radioisotopes; D005965:Glucuronates; C048351:tazadolene succinate