A Rapid Method to Estimate Hepatocyte Loss Due to Drug-Induced Liver Injury.

Autor: Chung JY; Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Korea., Longo DM; DILIsym Services, Inc., Research Triangle Park, North Carolina, USA., Watkins PB; Institute for Drug Safety Sciences, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2019 Mar; Vol. 105 (3), pp. 746-753. Date of Electronic Publication: 2018 Nov 02.
DOI: 10.1002/cpt.1254
Abstrakt: It is not currently possible to rapidly estimate the extent of hepatocyte loss during drug-induced liver injury (DILI). We used a proprietary mechanistic model (DILIsym) to estimate percentage hepatocyte loss due to DILI that resulted from four different patterns of serum alanine aminotransferase (ALT) over time: rapid onset and rapid decrease in ALT levels, moderate onset and moderate decrease in ALT levels, moderate onset and extended duration (over 1 month) of ALT elevations, and an ALT profile with multiple peaks. Using these data, we derived a novel parameter, P ALT  = ALT_AUC*Peak ALT 0.18 /10 5 ((IU/L) 2 *h), where AUC is area under the curve, that correlated well with hepatocyte loss estimates derived by DILIsym in patients with DILI due to six different hepatotoxic drugs. Although further validation will be required, the fact that P ALT can be derived rapidly using publicly available pharmacokinetic software may make it a useful parameter to improve the safety of drugs.
(© 2018 American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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