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2007
German

2006
Portuguese
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2005
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2003
Persian (Farsi)

Leonie Meemken and Laura Dickinson

In the field of the HIV-therapy, the most important interactions can occur during efflux/influx transport of drugs via transporters such as P-glycoprotein (P-gp) and metabolism by the cytochrome P450 enzyme system in the liver.

The cytochrome-P450 system consists of an array of various isoenzymes. Like many other drugs, protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are primarily metabolized by the isoenzyme CYP-3A4, mainly found in the liver and enterocytes of the gastrointestinal tract; therefore partial metabolism already starts in the intestine. The rate of drug metabolism can depend on genetic polymorphism of the isoenzymes involved. Thus, absence or reduced activity of the concerned enzymes can result in prolonged retention of a drug in the body.

Drugs that are metabolized by the cytochrome-P450 system can act in three different ways: as (1) a substrate, (2) an inhibitor or as (3) an inducer of the corresponding enzymes. Some drugs such as ritonavir (RTV), efavirenz (EFV) and nelfinavir (NFV) can show a combination of the three. The specific drug combination determines the predominant characteristic.

To evaluate possible drug interactions, a complete medication history including herbal extracts and recreational drugs is necessary. In particular, the use of drugs characterized by an increased potential for interactions, e. g. protease inhibitors, rifabutin, azole-antimycotics and anticonvulsants should be carefully observed. Due to the potential for increased risks of toxicity or virological failure, the possibility of drug interactions should always be taken into account. For more information about often complex drug interactions and for individual consultation refer to "www.ifi-interaction-hotline.com". Furthermore, a more comprehensive summary of interaction data can be found at "www.hiv-druginteractions.org".

Drug plasma concentrations depend on many different factors such as age, sex, liver and renal diseases and ethnic population. Thus, drug interactions are often difficult to predict. In many cases, dose adjustments in combination with therapeutic drug monitoring (TDM) can be very useful.

More? HIV Medicine 2007, Chapter 33: Download

HIV Medicine
15th edition
818 pages
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