Liver disease pharmacokinetic effects

Pharmacokinetics in specific populations to demonstrate the effect of age and disease on kinetics, for example, young, elderly, patients with renal failure, liver disease, cardiac failure... 

Rodighiero V. Effects of liver disease on pharmacokinetics. An update. Clin Pharmacokinet. 1999 37 399-431. 

Effects of liver disease on the pharmacokinetics of hepatically cleared drugs... 

Information regarding the pharmacokinetic/dynamic profile of a drug and its potential side effects allows yon to consider, from first principles, whether that drug is appropriate to use in a specific patient with liver disease, or whether it is best avoided. However, it is sometimes unnecessary to work solely from first principles other researchers may have already carried out and published some of this work for you. It is therefore useful to perform a literature search in order to identify any relevant studies that examine use of the drug in question in patients with similar types of liver disease to that of your patient. 

Irrespective of the pharmacokinetics of NSAIDs in patients with liver disease, the risks of adverse effects will outweigh the benefits of treatment in many patients. Side effects of note are gastrointestinal bleeding, reduction in glomerular filtration rate (GFR), inhibition... 

In a single-dose study examining the pharmacokinetics of sulindac and ibuprofen in 15 patients with alcoholic liver disease, no statistically significant effects were noted for ibuprofen elimination, half-life or AUC compared to the controls. However, there appeared to be delayed absorption in some patients [25]. 

The pharmacokinetics, pharmacodynamics and adverse effect profile of opioid analgesics are all relevant when considering the risks involved in using these drugs in patients with liver disease. There are also small variations between drugs in relation to pharmacokinetics and side effects, which may affect choice in certain circumstances. The decision to use opioids, the choice of opioid and the dose will therefore depend... 

End-organ sensitivity to opioids may be increased in liver disease, in terms of both analgesic properties and adverse effects, meaning that even if the pharmacokinetics of an opioid are not altered, the dose requirement in a patient with liver disease may be less. 

Some studies have suggested that the pharmacokinetics of morphine is altered in patients with liver disease, whereas other studies have found no such effect. The conflicting data are likely to be due to variable patient selection. 

Impaired renal function increases the incidence of ADRs for drugs that depend on the kidney for their elimination. Unlike liver disease, use of pharmacokinetic dosing principles can minimize the risk for adverse effects. 

Thus, to look at half-life only as a measure of, for instance, the effect of liver disease on drug pharmacokinetics is not sufficient, as a change in half-life can be caused by either a change in clearance or a change in volume of distribution. Furthermore, half-life may be unchanged in a particular disease state due to parallel changes in both E and CL. 

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