Adefovir Nucleoside reverse transcriptase inhibitors

The 2, 3 -dideoxynucleoside (ddN) analogues (Fig. 3) encompass a vast group of compounds that have been found active against HIV and HBV, although they have been primarily pursued for the treatment of HIV infections (AIDS). They are targeted at the HIV-associated reverse transcriptase (RT) and therefore also referred to as nucleoside reverse transcriptase inhibitors (NRTIs). They have to be distinguished from the nucleotide reverse transcriptase inhibitors (NtRTIs) such as adefovir (PMEA) and tenofovir (PMPA) (see above) which, like the NRTIs, act as chain... 

Adefovir is associated with a dose-dependent nephrotoxicity. The risk is low for treatment durations of up to 1 year at its recommended dosage for HBV but may rise in patients with preexisting renal dysfunction or in those treated for longer durations. Also, as with the antiretroviral nucleoside analogs (see Nucleoside Reverse Transcriptase Inhibitors), lactic acidosis and severe hepatomegaly with steatosis may occur. When coadministered with ibuprofen, the AUC of adefovir is increased by about 23%, apparently due to higher oral bioavailabilty. 

Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of medications approved for the management of HIV infection. They are structural analogues of nucleic acids. They undergo intracellular phosphorylation to a triphosphate metabolite and it is this metabolite that is pharmacologically active against reverse transcriptase. Drugs in this class include abacavir, adefovir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zidovudine. 

Non-nucleoside RTIs that do not require metabolic activation (eg, delavirdine and nevirapine, efavirenz, which are not myelosuppressants) and a nucleotide reverse-transcriptase inhibitor (adefovir) have been introduced. Resistance emerges rapidly if these drugs are used as individual agents for management of HIV infection. However, they may provide additive or synergistic activity against HIV if used in combination regimens with NRTIs and/or Pis. 

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