Apricitabine

Drugbox
IUPAC_name = 4-amino-1- [(2"R",4"R")-2-(hydroxymethyl)-1,3- oxathiolan-4-yl] pyrimidin-2(1"H")-one

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CAS_number=160707-69-7
CAS_supplemental=
ATC_prefix=
ATC_suffix=
ATC_supplemental=
PubChem=455041
DrugBank=
C=8 | H=11 | N=3 | O=3 | S=1
molecular_weight = 229.256 g/mol
bioavailability= 65 to 80%
protein_bound = < 4%
metabolism = To apricitabine triphosphate
elimination_half-life= 6 to 7 hours (triphosphate)
excretion = Renal
pregnancy_category =
legal_status = Investigational
routes_of_administration= Oral

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. [http://www.aidsmeds.com/archive/apricitabine_1593.shtml AIDSmeds.com - apricitabine ] ] As of 2008, apricitabine is in Phase IIb/III clinical trials, and has been granted fast track status by the United States Food and Drug Administration.cite web |url=http://www.aidsinfo.nih.gov/DrugsNew/DrugDetailT.aspx?int_id=415 |title=Apricitabine |date=March 13, 2007 |publisher=U.S. National Institutes of Health |work=AIDSinfo |accessdate=2008-08-29]

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.cite journal |author=Cahn P, Cassetti I, Wood R, "et al" |title=Efficacy and tolerability of 10-day monotherapy with apricitabine in antiretroviral-naive, HIV-infected patients |journal=AIDS |volume=20 |issue=9 |pages=1261–8 |year=2006 |month=June |pmid=16816554 |doi=10.1097/01.aids.0000232233.41877.63 |url=] 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. [cite conference |author=Cox S, Moore S, Southby J, "et al" |title=Safety profile of apricitabine, a novel NRTI, during 24-week dosing in experienced HIV-1 infected patients |booktitle=XVII International AIDS Conference (AIDS 2008) |date=August 5, 2008 |location=Mexico City |url=http://www.aids2008.org/Pag/Abstracts.aspx?SID=256&AID=4376 |id=Abstract TUAB0106 |accessdate=2008-08-29 [http://www.hivandhepatitis.com/2008icr/AIDS2008/docs/082208_c.html Lay summary] ] 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