US EPA

7433873 

Journal Article 

The relationship between chemical structure and the in vivo metabolism of an homologous series of n-alkyl carbamates 

Sargent, NS; Wood, SG; Upshall, DG; Bridges, JW; , 

1982 

Yes 

Journal of Pharmacy and Pharmacology
ISSN: 0022-3573 

34 

6 

367-372 

English 

6124619 

10.1111/j.2042-7158.1982.tb04731.x 

http://doi.wiley.com/10.1111/j.2042-7158.1982.tb04731.x
Exit
 

The metabolism and pharmacokinetics of carbonyl [14C] labelled ethyl, n-butyl, n-hexyl and n-octyl carbamates has been examined in rats after oral and intravenous administration. Hydrolysis of the carbamate group was a major metabolic fate, particularly of the more water soluble carbamates. Conversely, with increasing lipophilicity increasing amounts of omega-1 oxidation products were found both in plasma and urine. The plasma pharmacokinetic data could not be explained by a simple bi-exponential model, ethyl carbamate in particular showing unexpectedly persistent blood levels. A model has been proposed to explain the pharmacokinetic data for ethyl, n-butyl, n-hexyl and n-octyl carbamates. The essential features of this model are that carbamate is thought not to be in equilibrium between the peripheral and central compartment and that hydrolytic metabolism takes place in the peripheral compartment while oxidative metabolism to urinary metabolites occurs in the central compartment. 

animal experiment; carbamic acid butyl ester c 14; carbamic acid hexyl ester c 14; carbamic acid octyl ester c 14; drug blood level; drug comparison; drug metabolism; intravenous drug administration; lipophilicity; nonbiological model; oral drug administration; pharmacokinetics; rat; urethan c 14; Animal; Biotransformation; Carbamates; Chemistry, Physical; Injections, Intravenous; Intubation, Gastrointestinal; Kinetics; Lipids; Male; Rats; Rats, Inbred Strains; Solubility; Structure-Activity Relationship; Support, Non-U.S. Gov't; Time Factors