Details
Stereochemistry | RACEMIC |
Molecular Formula | C8H11N3O3S |
Molecular Weight | 229.256 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=NC(=O)N(C=C1)[C@H]2CO[C@@H](CO)S2
InChI
InChIKey=RYMCFYKJDVMSIR-RNFRBKRXSA-N
InChI=1S/C8H11N3O3S/c9-5-1-2-11(8(13)10-5)6-4-14-7(3-12)15-6/h1-2,6-7,12H,3-4H2,(H2,9,10,13)/t6-,7-/m1/s1
Apricitabine (ATC) is an investigational drug that was being studied for the treatment of HIV infection. Apricitabine belongs to a class (group) of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs block an HIV reverse transcriptase. By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body.
In vitro studies have shown that apricitabine appears to work on certain HIV strains against which other FDA-approved NRTIs, such as lamivudine (brand name: Epivir), may no longer work. Apricitabine shows antiviral activity in vitro against HIV-1 strains and clinical isolates with mutations in the reverse transcriptase that confer resistance to other NRTIs, including M184V, thymidine analogue mutations (TAMs), nucleoside-associated mutations such as L74V and certain mutations at codon 69. Apricitabine has shown activity in treatment-experienced HIV-1-infected patients with NRTI resistance (with M184V and up to five TAMs) as well as in treatment-naive patients. The study of apricitabine as an HIV medicine was discontinued in 2016. The company developing the drug decided to stop their clinical trials due to a lack of funding and a lack of interest in apricitabine’s early access program.
Originator
Approval Year
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4920 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121 |
400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
APRICITABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
9720 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121 |
800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
APRICITABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
11500 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121 |
1200 mg 2 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
APRICITABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
24100 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121 |
400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
APRICITABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
38100 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121 |
800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
APRICITABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
53200 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121 |
1200 mg 2 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
APRICITABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.45 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121 |
400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
APRICITABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2.69 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121 |
800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
APRICITABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1.91 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121 |
1200 mg 2 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
APRICITABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/19813775/ |
no | |||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/19813775/ |
no | |||
no | ||||
weak |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
likely | yes (co-administration study) Comment: Trimethoprim-sulfamethoxazole increased AUCinf and Cmax by 65.8% and 32.5% |
|||
likely | yes (co-administration study) Comment: Trimethoprim-sulfamethoxazole increased AUCinf and Cmax by 65.8% and 32.5% |
|||
no | ||||
no | ||||
no |
PubMed
Title | Date | PubMed |
---|---|---|
Selection and characterization of human immunodeficiency virus type 1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine. | 2000 May |
|
Efficacy and tolerability of 10-day monotherapy with apricitabine in antiretroviral-naive, HIV-infected patients. | 2006 Jun 12 |
|
Gateways to clinical trials. | 2007 Jan-Feb |
|
Effects of apricitabine and other nucleoside reverse transcriptase inhibitors on replication of mitochondrial DNA in HepG2 cells. | 2007 Oct |
|
Multiple-dose pharmacokinetics of apricitabine, a novel nucleoside reverse transcriptase inhibitor, in patients with HIV-1 infection. | 2008 |
|
Pharmacotherapy of pediatric and adolescent HIV infection. | 2009 Jun |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21054750
In this Phase II randomized, double-blind study, 51 treatment-experienced HIV-1-infected patients with the reverse transcriptase mutation M184V who were failing therapy which included lamivudine (3TC) were randomized to receive twice-daily 600 mg Apricitabine (ATC), 800 mg ATC or 150 mg 3TC for 21 days.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17542150
Apricitabine (ATC) showed similar activity (IC50: 10–50 uM) against isolates of
various group M HIV-1 clades, including A/G, B, C, D, A(E), D/F, F and H.
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DND9Y3G72C
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143338-12-9
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SUBSTANCE RECORD