Because the liver is central to the biotransformation of virtually all drugs and foreign substances, drug-induced livery injury is a potential complication of nearly every medication that is prescribed.
Hepatic ADRs
Because
the liver is central to the biotransformation of virtually all drugs and
foreign substances, drug-induced livery injury is a potential complication of
nearly every medication that is prescribed. The liver is the most common target
organ for toxicity encountered during the course of drug development (Ballet,
1997). Despite considerable progress in toxi-cological studies, the correlation
between liver toxi-city in animals and humans remains poor (Lumley, 1990). This
was highlighted by the tragic fialuri-dine trial, wherein potential
mitochondrial injury lead-ing to hepatic failure (resulting in 5 deaths and 2
liver transplantations among 15 treated patients) was not detected during
preclinical testing in rats, dogs, monkeys and woodchucks (infected with the
woodchuck hepatitis virus) treated with the drug for a month (McKenzie et al., 1995; Josephson, 1996).
Hepatotoxicity remains the principal cause of termination in clinical trials of
new chemical entities, accounting for one-third of such termina-tions. Adverse
hepatic reactions accounted for 24% of post-marketing withdrawals in the United
King-dom since 1975 and have been the leading cause of such withdrawals between
1975 and 2005. Further-more, the number of prescription drugs, including the
new molecular entities, on the market has increased dramatically from 5% in 1980
to 75% in 1998 (Friedman et al.,
1999). Hence, a larger number of agents now appear to contribute to the total
burden of drug-induced liver disease. Physician awareness of this constantly
changing pattern of drug-induced hepatotoxicity is essential for early
recognition.
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