Apricitabine
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| Clinical data | |
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| Routes of administration | Oral |
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| Pharmacokinetic data | |
| Bioavailability | 65 to 80% |
| Protein binding | < 4% |
| Metabolism | To apricitabine triphosphate |
| Elimination half-life | 6 to 7 hours (triphosphate) |
| Excretion | Renal |
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| Chemical and physical data | |
| Formula | C8H11N3O3S |
| Molar mass | 229.256 g/mol g·mol−1 |
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Apricitabine (INN, codenamed AVX754 and SPD754) is an experimental nucleoside reverse transcriptase inhibitor (NRTI) against HIV. It is structurally related to lamivudine and emtricitabine, and, like these, is an analogue of cytidine.
History
It was first developed by BioChem Pharma (where it was called BCH10618). BioChem Pharma was then sold to Shire Pharmaceuticals (where apricitabine was called SPD754). Shire then sold the rights to develop the drug to Avexa Pharmaceuticals, an Australian pharmaceutical company.[1] As of 2009[update], apricitabine has closed its phase III clinical trial[2], and has been granted fast track status by the United States Food and Drug Administration.[3]
Avexa announced its decision to end work on apricitabine in May 2010, which Avexa spent more than A$100 million ($90 million) developing and was in the final of three stages of patient studies usually needed for U.S. regulatory approval. Grounds for the shutdown included the inability to find commercial partners for global licencing, concerns about legal protections of the drug in the US market, and difficulty confirming the effectiveness of the drug in patients where other retroviral drugs masked key indicators.[4] Accordingly, the drug is not currently available on the market.
Dosage
As a monotherapy, 1200 mg apricitabine per day reduced the viral load by up to 1.65 logs (45 fold) in a small, 10-day randomized controlled trial.[5]
Adverse effects
Apricitabine appears to be well tolerated. The most common side effects associated with its use were headache (although there was no significant difference between participants who took apricitabine and those given a placebo), nasal congestion, and muscle pain.[5] In a six-month trial, common adverse effects were nausea, diarrhea, elevated blood levels of triglycerides, and upper respiratory infection—similar to those of lamivudine; apricitabine was not associated with abnormal lipase levels, bone marrow suppression, or liver and kidney toxicity.[6] No patients in either study had to stop taking apricitabine because of side effects.
Drug resistance
In vitro, apricitabine was effective against NRTI-(lamivudine and zidovudine)-resistant viruses.
In early studies, no mutations causing drug resistance were observed. Newer trials showed that apricitabine may induce K65R mutations, resulting in resistance against didanosine and tenofovir.[1]
References
- ^ a b AIDSmeds.com - apricitabine
- ^ Avexa Closes ATC's Phase III Trial To Evaluate Data
- ^ "Apricitabine". AIDSinfo. U.S. National Institutes of Health. March 13, 2007. Retrieved 2008-08-29.
- ^ [1]
- ^ a b Cahn P, Cassetti I, Wood R; et al. (2006). "Efficacy and tolerability of 10-day monotherapy with apricitabine in antiretroviral-naive, HIV-infected patients". AIDS. 20 (9): 1261–8. doi:10.1097/01.aids.0000232233.41877.63. PMID 16816554.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Cox S, Moore S, Southby J; et al. (August 5, 2008). "Safety profile of apricitabine, a novel NRTI, during 24-week dosing in experienced HIV-1 infected patients". XVII International AIDS Conference (AIDS 2008). Mexico City. Abstract TUAB0106. Retrieved 2008-08-29.
{{cite conference}}: Explicit use of et al. in:|author=(help); Unknown parameter|booktitle=ignored (|book-title=suggested) (help)CS1 maint: multiple names: authors list (link) Lay summary