Apricitabine

Apricitabine

File:Apricitabine.svg
Systematic (IUPAC) name
4-amino-1-[(2R,4R)-2-(hydroxymethyl)-1,3- oxathiolan-4-yl]pyrimidin-2(1H)-one
Clinical data
Routes of administration	Oral
Legal status
Legal status	Investigational
Pharmacokinetic data
Bioavailability	65 to 80%
Protein binding	< 4%
Metabolism	To apricitabine triphosphate
Biological half-life	6 to 7 hours (triphosphate)
Excretion	Renal
Identifiers
CAS Number	160707-69-7
ATC code	none
PubChem	CID 455041
Chemical data
Formula	C8H11N3O3S
Molar mass	229.256 g/mol[[]]

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. As of 2009, apricitabine has closed its phase III clinical trial, and has been granted fast track status by the United States Food and Drug Administration. 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.

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.

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. 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. 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.

References

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