A clinical pharmacologist's view of drug hepatotoxicity

Dujovne, Carlos A.

doi:10.1016/s0031-6989(77)80049-0

Cited by 8 publications

(1 citation statement)

References 66 publications

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“…One reason for this has been the limited knowledge about the activity of drug-metabolizing enzymes in human livers. This is rather surprising since the needle biopsy is a routine method to confirm diagnosis in patients with liver diseases (25,26) and with druginduced hepatic injury (27) and the use of micromethods (23,28) makes it possible to determine the activity of drugmetabolizing enzymes and the hepatic histology in the same specimen. Moreover, plasma drug clearance is a quantitative measure ofliver function (29,30) and a useful tool for drug selection for patients with liver damage (31,32).…”

Section: Discussionmentioning

confidence: 99%

Relationship between in vivo and in vitro drug metabolism in man

Sotaniemi

Pelkonen

Ahokas

et al. 1978

European Journal of Drug Metabolism and Pharmacokinetics

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450, liver drug metabolism, in vivo in vitro drug metabolism SUMMARY Relationship between in vivo and in vitro drug metabolism was investigated in 200 consecutive patients with diagnostic liver needle biopsy by comparing the cytochrome P-450 (P-450) content in biopsies with the elimination kinetics of antipyrine. P-450 level in livers varied from 0.5 to 32.5 nmole/g, it was increased in subjects treated with enzyme inducing drugs and reduced in patients with degenerative parenchymal changes in the liver. Antipyrine metabolism also varied markledy, the half-life ranged from 2.2 to 54.4 hrs and the clearance from 3.5 to 142.4 ml/min. Rapid drug metabolism was associated with subjects with normal liver or with slight liver changes in case they were also treated with known inducers whereas reduced antipyrine metabolism was seen in subjects with degenerative liver changes. P-450 content in biopsies was related to the kinetic parameters of antipyrine: correlation between P-450 in livers and the drug clearance was linear whereas a non-linear relationship between P-450 and plasma half-life was obtained. The results demonstrate a relationship between in vivo and in vitro parameters of drug metabolism in man and show the importance of liver parenchymal changes and drug therapy as factors influencing hepatic drug metabolism.

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