Delaviridine

Delavirdine should not be used in combination with drugs that are CYP3A4 substrates such as pimozide, midazolam, triazolam, amiodarone, propafenone and ergot derivatives. Inducers of the hepatic P-450 system, rifampin, rifabutin, pheno-barbital, phenytoin or carbamazepine, should not be used in combination with delaviridine. It also increases the plasma levels of HIV protease inhibitors. 

The newer agents (NNRTIs) such as delaviridine, efavirenz, and nevirapine directly inhibit the reverse transcriptase enzyme by binding to the enzyme s active (catalytic) site and preventing this enzyme from converting viral RNA to viral DNA.37,94 Thus, these agents offer an alternative way to impair reverse transcriptase function and prevent viral replication. 

CYP3A4 Inhibition Amiodarone, clarithromycin, erythromycin, cimetidine, cyclosporine, fluoxetine fluvoxamine, itraconazole, ketoconazole, nefazodone, verapamil, diltiazem HIV antivirals delaviridine, indanavire, nelfmavire, ritonavire, sequinavire Atorvastatin Lovastatin Simvastatin ... 

There are also now a number of non-nucleotide reverse transcriptase inhibitors and the most useful of these are nevirapine (Viramune, 1996) and delaviridine (Rescriptor, 1997), which appear to act at an allosteric site close to the active site of RT. This means that they block the subtle (and apparently essential) changes in the three-dimensional structure that occur when nucleotide substrates bind to the active site of RT. 

Delaviradine is rapidly absorbed by oral administration and peak plasma concentration was obtained in 1 hour. Administration of delaviridine at 400 mg three times daily resulted in peak plasma concentration of 45 mM. The single dose bioavailability of delaviridine tablets relative to oral solution was approximate 85%. The 50% inhibitory concentration for delavirdine against RT activity was 6.0 nM. Delaviridine is extensively bound to plasma protein (-98%). It is metabolized to its N-desisopropyl metabolite in liver, and the pharmacokinetics is nonlinear. Clarithromycin, rifabutin, or ergot alkaloid derivatives are predicted to increase plasma concentration of delaviridine. Skin rashes are the major side effect of delavirdine therapy. Cross-resistance between delavidine and Pis, such as indinavir, nelfinavir, ritonavir, and saquinavir, is unlikely because of action on different enzyme targets. 

Freimuth WW. Delaviridine mesylate, a potent nonnucleoside FIIV-1 reverse transcriptase inhibitor. Adv Exp Med Biol 1996 394 279-289. 

A few indole-based compounds are active against viruses (Scheme 24). The non-nucleoside reverse transcriptase inhibitor delaviridine (163) is used in antiretroviral therapy [150]. The blue-green alga Dichothrix baueriana has yielded bauerine B (164), a dichloro p-carboline active againstherpes simplex virus type 1 [169]. Seeds of the plant Solarium indicum have yielded the new coumarinolignoid indicumine B (165), which possesses anti-hepatitis B... 

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