title: A kinetic evaluation of 14CO2 in expired air after 14C-methacetin administration in rats, used for the in vivo study of the metabolism of drugs.
abstract: The pharmacokinetics of the blood level and the patterns of 14CO2 exhalation were determined simultaneously following i.v. administration of 14C-methacetin to the conscious rat. The pattern of exhalation of 14CO2 did not parallel the biexponential decline of radioactivity in the blood and a delay of 30-40 min preceded the maximal rate of 14CO2 exhalation. The total radioactivity exhaled remained constant at 56 +/- 4.5% (SD) of the applied dose throughout a tenfold dose range of methacetin (0.6, 4.0 and 6.0 mg/kg i.p.), administered to groups of three rats each and measured over a period of 4 hours. The pattern of radiolabel exhalation was biexponential with the low dose, linear with the medium dose and convex with the high dose. Although the total fraction of the label expired after 4 hours remained constant, the rates of exhalation at the higher dosages exhibited saturation type kinetics. At the higher dosage, since the pattern of 14CO2 exhalation did not accurately reflect the decline of methacetin seen in blood, one of the steps occurring between the demethylation process and the production of expired CO2 appears to be rate limiting. Significant increases in the amount of 14CO2 exhaled within 1 hour were obtained by pretreatment with phenobarbital, rifampicin and 3-methylcholanthrene. Again the proportion of radiolabel expired in 4 hours remained constant. Acute hepatic injury produced by pretreatment with graded doses of carbon tetrachloride resulted in graded reductions in the amount of 14CO2 exhaled in the first hour, although the total amount exhaled during the 4 hour collection period did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000081:Acetamides / Q000378:metabolism*; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002251:Carbon Tetrachloride / Q000633:toxicity; D003640:Dealkylation; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D007700:Kinetics; D008107:Liver Diseases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration
chemical_list: D000081:Acetamides; D002250:Carbon Radioisotopes; D000632:Aminopyrine; C035495:methacetin; D002245:Carbon Dioxide; D002251:Carbon Tetrachloride