Emtricitabine exhibits in vitro efficacy against clinical isolates of HIV-1 as well as laboratory strains of HIV-1 and HIV-2. EC50, or the 50% effective concentration, varies between 0.002 to 1.5 μmol/L based on the cell line and virus isolate employed. When paired with didanosine or zalcitabine, emtricitabine is active in vitro and synergizes with stavudine and zidovudine in vitro [1].

Emtricitabine was used in toxicity research related to reproduction and development. The daily area under the curve (AUC0→24) for exposure to pregnant animals at oral dosages up to 1000 mg/kg/day once daily is around 60- to 120-fold (mouse to rabbit), greater than the recommended amount for humans ( 200 mg). Emtricitabine had no effect on sperm count, early embryonic development, or fertility in a mouse fertility research. Studies on the embryofetal toxicity of mice and rabbits did not reveal a higher prevalence of abnormalities. Emtricitabine had no effect on the development or fertility of F1 offspring in prenatal or postnatal trials conducted in mice. According to these findings, emtricitabine has a favorable preclinical safety profile for reproduction [2].

Absorption, Distribution and Excretion
Emtricitabine reaches a Cmax of 1.8±0.7µg/mL with a Tmax of 1-2 hours, and has an AUC of 10±3.1µg\*hr/mL. The bioavailability of emtricitabine capsules is 93% and the bioavailability of the oral solution is 75%. Taking emtricitabine with food decreases the Cmax by 29%.[L9019
Emtricitabine is 86% recovered in the urine and 14% recovered in feces. 13% of the dose is recovered in the urine as metabolites; 9% as 3'-sulfoxide diastereomers and 4% as 2'-O-glucuronide.
The apparent central volume of distribution is 42.3L and the peripheral volume of distribution is 55.4L.
Emtricitabine has an apparent elimination rate of 15.1L/h. This rate is closely linked to creatinine clearance.
Emtricitabine is rapidly and extensively absorbed following oral administration with peak plasma concentrations occurring at 1 to 2 hours post-dose. Following multiple dose oral administration of emtriva to 20 HIV-infected subjects, the (mean + or - SD) steady state plasma emtricitabine peak concentration (Cmax) was 1.8 + or 0.7 ug/mL and the area under the plasma concentration-time curve over a 24-hour dosing interval (AUC) was 10.0 + or - 3.1 hr/ug/mL. The mean steady state plasma trough concentration at 24 hours post-dose was 0.09 ug/mL. The mean absolute bioavailability of emtriva was 93%.
In vitro binding of emtricitabine to human plasma proteins was <4% and independent of concentration over the range of 0.02 to 200 ug/mL. At peak plasma concentration, the mean plasma to blood drug concentration ratio was approximately 1.0 and the mean semen to plasma drug concentration ratio was approximately 4.0.
Time to peak concentration: 1 to 2 hours post dose
Emtricitabine is distributed into human milk in low concentrations.
For more Absorption, Distribution and Excretion (Complete) data for EMTRICITABINE (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Emtricitabine is approximately 86% unmetabolized. Approximately 9% of a dose is metabolized to 3'-sulfoxide diastereomers, 4% to the 2'-O-glucuronide, and a minor amount is converted to 5-fluorocytosine.
The biotransformation of emtricitabine includes oxidation of the thiol moiety to form the 3'-sulfoxide diastereomers (approximately 9% of dose) and conjugation with glucuronic acid to form 2'-O-glucuronide (approximately 4% of dose). No other metabolites were identifiable. Emtricitabine is not metabolized by liver enzymes.

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Biological Half-Life
The half life of emtricitabine is approximately 10 hours.
The plasma emtricitabine half-life is approximately 10 hours.

Hepatotoxicity
There is little evidence for direct hepatotoxicity of emtricitabine and it has not been specifically implicated in cases of lactic acidosis with steatosis and hepatic failure. However, patients with chronic hepatitis B can experience a flare of the underlying hepatitis during emtricitabine therapy. These flares occur either at the start therapy (treatment flares), with the development of antiviral resistance (breakthrough flares), or when therapy is abruptly stopped (withdrawal flares). Treatment flares occur in 5% to 10% of patients, are usually transient and asymptomatic, and rarely require dose modification or discontinuation of therapy. In contrast, withdrawal flares occur in 15% to 30% of patients, but can be symptomatic and severe, in rare instances (~1%) leading to acute liver failure, death or requirement for emergency liver transplantation. Patients who develop emtricitabine resistance often have relapse of disease activity after the appearance of the mutant HBV strain and rise in HBV DNA levels; this relapse can initially be severe and associated with symptoms and jaundice.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Emtricitabine has been relatively well studied during breastfeeding and it is sometime used in treating HIV-positive mothers who are breastfeeding. Achieving and maintaining viral suppression with antiretroviral therapy decreases breastfeeding transmission risk to less than 1%, but not zero. Individuals with HIV who are on antiretroviral therapy with a sustained undetectable viral load and who choose to breastfeed should be supported in this decision. If a viral load is not suppressed, banked pasteurized donor milk or formula is recommended.
For use in treating maternal hepatitis B, no difference exist in infection rates between breastfed and formula-fed infants born to hepatitis B-infected women, as long as the infant receives hepatitis B immune globulin and hepatitis B vaccine at birth. Mothers with hepatitis B are encouraged to breastfeed their infants after their infants receive these preventative measures. With HIV pre-exposure prophylaxis with tenofovir 200 mg and emtricitabine 300 mg, infants receive only about 0.5% of a therapeutic dose of emtricitabine. During long-term maternal use of emtricitabine 200 mg daily, breastfed infants usually have undetectable blood concentrations.
◉ Effects in Breastfed Infants
In a study of 50 infants breastfed by HIV-negative women who were given pre-exposure prophylaxis daily with the combination of tenofovir disoproxil fumarate 300 mg and emtricitabine 200 mg by directly observed therapy for 10 days, 2 infants reportedly had diarrhea lasting 2 to 3 days. No other side effects were reported.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Emtricitabine is <4% bound to plasma proteins, mainly serum albumin.

[1]. Emtricitabine, a new antiretroviral agent with activity against HIV and hepatitis B virus. Clin Infect Dis.?2006 Jan 1;42(1):126-31.

[2]. Combined Medication of Antiretroviral Drugs Tenofovir Disoproxil Fumarate, Emtricitabine, and Raltegravir Reduces Neural Progenitor Cell Proliferation In Vivo and In Vitro. J Neuroimmune Pharmacol. 2017 Dec;12(4):682-692.

[3]. Szczech GM, Wang LH, Walsh JP, Reproductive toxicology profile of emtricitabine in mice and rabbits. Reprod Toxicol. 2003 Jan-Feb;17(1):95-108.

[4]. Effect of the Anti-retroviral Drugs Efavirenz, Tenofovir and Emtricitabine on Endothelial Cell Function: Role of PARP. Cardiovasc Toxicol. 2017 Jan 3. [Epub ahead of print].

Emtricitabine is an organofluorine compound that is 5-fluorocytosine substituted at the 1 position by a 2-(hydroxymethyl)-1,3-oxathiolan-5-yl group (2R,5S configuration). It is used in combination therapy for the treatment of HIV-1 infection. It has a role as an antiviral drug and a HIV-1 reverse transcriptase inhibitor. It is a pyrimidone, an organofluorine compound, a monothioacetal and a nucleoside analogue.
Emtricitabine (brand name: Emtriva) is a prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection in adults, children, and infants. Emtricitabine is always used in combination with other HIV medicines.
Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) indicated for the treatment of HIV infection in adults or combined with [tenofovir alafenamide] for the prevention of HIV-1 infection in high risk adolescents and adults. Emtricitabine is a cytidine analogue. The drug works by inhibiting HIV reverse transcriptase, preventing transcription of HIV RNA to DNA. Emtricitabine was granted FDA approval on 2 July 2003.
Racivir, also known as RCV, is an oxothiolane nucleoside reverse transcriptase inhibitor similar to emtricitabine and lamivudine. Racivir is a 50:50 mixture of [emtricitabine] and its positive enantiomer. Racivir has been used in trials studying the prevention of HIV Infections.
Emtricitabine is a Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor. The mechanism of action of emtricitabine is as a Nucleoside Reverse Transcriptase Inhibitor.
Emtricitabine is a nucleoside analogue and reverse transcriptase inhibitor used in combination with other agents for treatment and prevention of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Emtricitabine does not appear to be a significant cause of drug induced liver injury, but may cause flares of disease in patients with underlying chronic hepatitis B virus (HBV) infection.
Emtricitabine is a synthetic fluoro derivative of thiacytidine with potent antiviral activity. Emtricitabine is phosphorylated to form emtricitabine 5'-triphosphate within the cell. This metabolite inhibits the activity of human immunodeficiency virus (HIV) reverse transcriptase both by competing with the natural substrate deoxycytidine 5'-triphosphate and by incorporation into viral DNA causing a termination of DNA chain elongation (due to the lack of the essential 3'-OH group).
A deoxycytidine analog and REVERSE TRANSCRIPTASE INHIBITOR with antiviral activity against HIV-1 and HEPATITIS B viruses. It is used to treat HIV INFECTIONS.

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Drug Indication
Emtricitabine is indicated in combination with other medications for the treatment of HIV-1 infections; treatment of HIV-1 infections in pediatric patients 25-35kg, treatment of HIV-1 infections in adult patients ≥35kg, for pre exposure prophylaxis of HIV-1 in adolescent and adult patients excluding those who have receptive vaginal sex; treatment of HIV-1 infections in pediatric and adult patients ≥17kg, pre exposure prophylaxis in adolescents and adults ≥35kg; treatment of HIV-1 in patients ≥12 years and ≥35kg; treatment of HIV-1 in patients weighing ≥35kg; treatment of HIV-1 in patients weighing ≥25kg; and treatment of HIV-1 in patients weighing ≥40kg.
FDA Label
Emtriva is indicated for the treatment of HIV-1 infected adults and children in combination with other antiretroviral agents. This indication is based on studies in treatment-naive patients and treatment-experienced patients with stable virological control. There is no experience of the use of Emtriva in patients who are failing their current regimen or who have failed multiple regimens. When deciding on a new regimen for patients who have failed an antiretroviral regimen, careful consideration should be given to the patterns of mutations associated with different medicinal products and the treatment history of the individual patient. Where available, resistance testing may be appropriate.

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Mechanism of Action
Emtricitabine is a cytidine analog which, when phosphorylated to emtricitabine 5'-triphosphate, competes with deoxycytidine 5'-triphosphate for HIV-1 reverse transcriptase. As HIV-1 reverse transcriptase incorporates emtricitabine into forming DNA strands, new nucleotides are unable to be incorporated, leading to viral DNA chain termination. Inhibition of reverse transcriptase prevents transcription of viral RNA into DNA, therefore the virus is unable to incorporate its DNA into host DNA and replicate using host cell machinery. This reduces viral load.
Emtricitabine, a synthetic nucleoside analog of cytosine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of the HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in chain termination. Emtricitabine 5'-triphosphate is a weak inhibitor of mammalian DNA polymerase alpha, beta, epsilon and mitochondrial DNA polymerase gamma.

C8H10FN3O3S

247.25

247.042

143491-57-0

Emtricitabine-13C,15N2;1217820-69-3;Emtricitabine-15N,d2;2714436-53-8

60877

White to off-white solid powder

1.8±0.1 g/cm3

443.3±55.0 °C at 760 mmHg

136-140°C

221.9±31.5 °C

0.0±2.4 mmHg at 25°C

1.731

-0.41

2

5

2

16

374

2

C1[C@H](O[C@H](S1)CO)N2C=C(C(=NC2=O)N)F

XQSPYNMVSIKCOC-NTSWFWBYSA-N

InChI=1S/C8H10FN3O3S/c9-4-1-12(8(14)11-7(4)10)5-3-16-6(2-13)15-5/h1,5-6,13H,2-3H2,(H2,10,11,14)/t5-,6+/m0/s1

4-amino-5-fluoro-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one

BW-1592; BW1592; BW 1592; trade names: Coviracil; Emtriva; Racivir; (-)-FTC; W-201247; W-201248; E1007; 24229-EP2298783A1; 24229-EP2314590A1; AB01275429-01; 3B2-0188

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (10.11 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (10.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)