Therapeutic Drug Monitoring of the HIV/AIDS Drugs Abacavir, Zidovudine, Efavirenz, Nevirapine, Indinavir, Lopinavir, and Nelfinavir

Combination therapy with antiretroviral drugs is used for the treatment of patients infected with the human immunodeficiency virus. To achieve optimal drug concentrations for viral suppression and avoidance of drug toxicity, monitoring of drug levels has been considered essential.

Researchers in Graz, Austria set up an analytical procedure for monitoring the plasma concentrations of a total of seven drugs: abacavir (Ziagen), zidovudine (Retrovir), efavirenz (Sustiva), nevirapine (Viramune), indinavir (Crixivan), lopinavir (Kaletra), and nelfinavir (Viracept).

The plasma samples were liquid/liquid extracted and subjected to high-performance liquid chromatography (HPLC) analysis. The compounds were monitored by ultraviolet detection: indinavir, lopinavir, and nelfinavir at 215 nm; efavirenz at 254 nm, and abacavir, zidovudine, and nevirapine at 266 nm.

Two different extraction procedures and two different HPLC eluents on a C₈ reversed-phase HPLC column were used to monitor all seven compounds. Under steady state conditions, the plasma concentrations of antiviral drugs in 175 patients were correlated with the time after the last dosing to define the peak or trough levels.

Due to the short plasma elimination half-life of abacavir and zidovudine, only peak levels could be determined for these compounds, whereas both peak and trough levels could be assessed for the other compounds because of a longer plasma elimination half-life.

The mean peak concentrations (µg/ml) were 0.69 for abacavir and 0.57 for zidovudine; the mean peak/trough concentrations (µg/ml) were 2.07/1.32 for efavirenz, 2.43/2.23 for nevirapine, 5.48/1.08 for indinavir, 4.69/3.51 for lopinavir, and 3.54/1.45 for nelfinavir.

The described analytical method offers a broad-spectrum monitoring of plasma levels of antiretroviral drugs.

11/26/03