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K J Netter

Publications and source records attributed to K J Netter.

114 records · Page 7Linked to original sources
PubMedDate not supplied

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.

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)

Acetamides↗
PubMedDate not supplied

Indications for nitrosamide formation from the mushroom poison gyromitrin by rat liver microsomes.

1. N-Methyl-N-formylhydrazine, formed by hydrolysis from gyromitrin, the main toxin of the edible mushroom Gyromitra esculenta, lowers the cytochrome P-450 concn. in liver microsomes after its application to rats. 2. This decrease can be intensified by pretreatment of the rats with phenobarbital but not by induction with 3-methylcholanthrene. 3. The effect of methylformylhydrazine can be abolished in relation to inhibitor-treated controls by prior administration of SKF 525-A but not metyrapone. 4. After addition of methylformylhydrazine to liver microsomes of rats pretreated with phenobarbital in the presence of a NADPH-regenerating system and O2 a metabolite was formed with a time dependent difference spectral max. at 425 nm. When subsequently the microsomal mixture was reduced by addition of NADPH or sodium dithionite, a new spectrum was obtained with a max. at 447 nm, which decreased within a few minutes with a slight blue-shift. 5. The cytochrome P-450 mediated oxidation of methylformylhydrazine to a hydroxylamine derivative and further to a nitrosamide, is discussed in relation to its importance for the biological action of the hydrazine. This nitrosamide formation may be the reason for the known hepatocarcinogenicity of methylformylhydrazine.

Acetaldehyde↗
PubMedDate not supplied

Rat hepatic microsomal cytochrome(s) P-450 induced by polybrominated biphenyls.

Various parameters have been measured in order to characterize the type of cytochrome(s) P-450 induced by a single ip injection of polybrominated biphenyls (PBB's), 150 mg/kg, given to female rats. The ratio of the 427/455-nm peaks in the microsomal ethylisocyanide difference spectra showed a gradual increase with time after treatment with PBB's. Inhibition studies of aryl hydrocarbon hydroxylase and ethoxycoumarin O-de-ethylase and alpha-naphthoflavone and metyrapone also showed changes in the qualitative nature of these enzymes after treatment with PBB's. Both the high- and low-affinity KM values for ethoxycoumarin O-de-ethylase decreased in magnitude from 0.240 and 0.083 micrometer at 24 hr to 0.188 and 0.042 micrometer, respectively, at 192 hr after treatment with PBB's. Sodium dodecyl sulfate-gel electrophoresis failed to demonstrate a 3-methylcholanthrene-like pattern of hemoprotein at any time after treatment with PBB's. We conclude that while PBB's have some of the properties of a mixed inducer they do not have all of the properties of both phenobarbital and 3-methylcholanthrene, and the PBB's may represent a new class of inducing agents.

Animals↗