Tenofovir Adefovir

However, acyclic nucleotide analogs (acyclic nucleoside phosphonates) have been developed, which carry one phosphonate moiety and require only the two subsequent phosphorylation steps (De Clercq et al. 1978). Independent of virus-encoded kinases, they display a broader spectrum of efficacy. This class comprises important drugs against HIV (tenofovir) and HBV (adefovir, tenofovir), as well as cidofovir, which is approved for use against CMV retinitis, but also displays an exceptionally broad efficacy profile against many herpesviruses, adenovirus, poxviruses, and papillomaviruses (De Clercq and Holy 2005). 

Acute tubular necrosis (exogenous toxins) Aminoglycosides, amphotericin, cisplatin, radiocontrast agents, methoxyflurane, outdated tetracyclines, cephalosporins, mithramycin, calcineurin inhibitors, pentamidine, IVIG, ifosfamide, zoledronate, cidofovir, adefovir, tenofovir FENa>2%, UOsm <350, urinary sediment contains granular casts, renal epithelial cells... 

Antiretroviral agents Acyclovir, adefovir, tenofovir, indinavir Acute interstitial nephritis, tubular cell toxicity... 

The prototype member of the ANPs is (5)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)adenine (HPMPA) (Fig. 2), first described for its broad-spectrum anti-DNA virus activity in 1986 (De Clercq et al. 1986). Then followed by the description of various other acyclic nucleoside phosphonates in 1987 (De Clercq et al. 1987). At present three acyclic nucleoside phosphonates have been licensed for clinical use cidofovir, adefovir, and tenofovir (Fig. 2). 

After me ANPs (i.e., cidofovir, adefovir, and tenofovir) have been released (intra-or extraceUularly) from their prodrugs through the mtervention of infra- or extracellular esterases, they need only two phosphorylation steps to be converted to their active metabolites (i.e., HPMPCpp, PMEApp, and PMPApp), which will then compete with the natural substrates (dCTP for HPMPCpp, and dATP for PMEApp and PMPApp) for incorporation into me viral DNA (Fig. 6a). 

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... 

All the nucleoside (and nucleotide) analogues that have entered the clinic for the treatment of HBV infections (i.e., nucleoside analogues lamivudine, entecavir, tel-bivudine nucleotide analogues adefovir and tenofovir) are fairly well tolerated without side effects that would preclude their long-term usage. The nucleoside analogues in (pre)clinical development for the treatment of HCV infections are not yet sufficiently advanced to assess their tolerability and/or safety. 

In addition to the NRTI lamivudine (3TC) and the NtRTI adefovir dipivoxU and tenofovir disoproxil fumarate (which has been recently licensed for the treatment of chronic hepatitis B), two other nucleoside analogues, that is, entecavir and L-dT (tel-bivudine) (Fig.4aa), have been licensed for the treatment of HBV infections. Two other compounds 3 -Val-L-dC (valtorcitabine) and L-FMAU (clevudine) (Fig. 4aa) are in clinical development for the treatment of HBV infections, and yet two other compounds, that is, racivir and elvucitabine (Fig. 3), yield potential for the treatment of both HBV and HIV infections. 

De Clercq E (2006) From adefovir to Atripla via tenofovir, Viread and Truvada. Future Virol 1 709-715... 

Add adefovir or tenofovir Add lamivudine or telbivudine Switch to or add adefovir or tenofovir Add adefovir or tenofovir... 

Other drugs that are commonly implicated in causing ARF include acyclovir, adefovir, carboplatin, cidofovir, cisplatin, foscarnet, ganciclovir, indinavir, methotrexate, pentamidine, ritonavir, sulfinpyrazone, and tenofovir.45... 

Adefovir, cidofovir, tenofovir Radiographic contrast media... 

Drugs eliminated by the kidneys Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase serum concentrations of tenofovir and/or the coadministered drug. Some examples include, but are not limited to, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, and valganciclovir. Drugs that decrease renal function also may increase serum concentrations of tenofovir. 

Several anti-HBV agents have anti-HIV activity as well, including lamivudine, adefovir dipivoxil, and tenofovir. Emtricitabine, an antiretroviral NRTI, is under clinical evaluation for HBV treatment. Because NRTI agents may be used in patients co-infected with HBV and HIV, it is important to note that acute exacerbation of hepatitis may occur upon discontinuation or interruption of these agents. 

DeClercq E. 2003. Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir and tenofovir in treatment of DNA virus and retrovirus infections. Clin Microbiol Rev. 16 ... 

Although initially and abortively developed for treatment of HIV infection, adefovir has been recently approved, at lower and less toxic doses, for treatment of HBV infection. Like tenofovir (see Antiretroviral Agents), adefovir is a nucleotide analog. As an analog of adenosine monophosphate, adefovir is phosphorylated by cellular kinases to the active disphosphate metabolite it then competitively inhibits HBV DNA polymerase and results in chain termination after incorporation into the viral DNA. 

Imaoka T, Kusuhara H, Adachi M, et al. Functional involvement of multidrug resistance associated protein 4 (MRP4/ABCC4) in the renal elimination of the antiviral drugs, adefovir and tenofovir. Mol Pharmacol 2007 71 619-627. 

TENOFOVIR ADEFOVIR, CIDOFOVIR t adverse effects T plasma levels, competition for renal excretion via organic anion transporter Monitor renal function weekly... 

ADEFOVIR DIPIVOXIL 1. ANTIBIOTICS -aminoglycosides, vancomycin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - cidosporin, tacrolimus 3. ANTIFUNGALS-amphotericin, 4. ANTIPROTOZOALS-pentamidine 5. ANTIVIRALS - cidofovir, foscarnet sodium, tenofovir Possible t efficacy and side-effects Competition for renal excretion Monitor renal function weekly... 

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. 

Oats Sitagliptin, cimetidine, ibuprofen, quinapril, indapamide, adefovir, cidofovir, tenofovir, cephalosporin, torsemide... 

The therapeutic armementarium in this field is enlarging with promising results but at the expense of viral resistance and cost.The drugs used in HBV treatment are mainly interferons (mostly pegylated), and nucleos(t)ide analogs (Lamivudine, Adefovir and the more recent ones Telbivudine, Entecavir and Tenofovir). Different... 

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