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| | Lamivudine Basic information |
| | Lamivudine Chemical Properties |
| Melting point | 177 °C | | alpha | D21 -135° (c = 0.38 in methanol) | | Boiling point | 475.4±55.0 °C(Predicted) | | density | 1.73±0.1 g/cm3(Predicted) | | refractive index | -142 ° (C=1, MeOH) | | Fp | 9℃ | | storage temp. | 2-8°C | | solubility | water: soluble10mg/mL, clear | | form | powder | | pka | 13.83±0.10(Predicted) | | color | white to beige | | Water Solubility | 70g/L(temperature not stated) | | Merck | 14,5352 | | BCS Class | 1,3 | | Stability: | Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month. | | InChIKey | JTEGQNOMFQHVDC-NKWVEPMBSA-N | | CAS DataBase Reference | 134678-17-4(CAS DataBase Reference) | | EPA Substance Registry System | 2(1H)-Pyrimidinone, 4-amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]- (134678-17-4) |
| | Lamivudine Usage And Synthesis |
| Description | Lamivudine is a new generation orally active nucleoside analog launched in the U.S.A. for use in combination with zidovudine (AZT) as a first-line therapy for patients with HIV infection. Lamivudine is rapidly converted to phosphorylated metabolites in the body which act as inhibitors and chain terminators of HIV reverse transcriptase (RT), the enzyme required for the replication of the HIV genome. Lamivudine has similar inhibitory potency to RT as AZT but is 10 times less toxic and is active against AZT-resistant strains of HIV. | | Chemical Properties | White Crystalline Powder | | Originator | BioChem Pharma (Canada) | | Uses | Lamivudine is used along with other medications to treat human immunodeficiency virus (HIV) infection in adults and children 3 months of age and older.
Lamivudine (Epivir-HBV) is used to treat hepatitis B infection.
Lamivudine is in a class of medications called nucleoside reverse transcriptase inhibitors (NRTIs). It works by decreasing the amount of HIV and hepatitis B in the blood. | | Synthesis | Aqueous hydrochloric acid (6N, 30 ml) was slowly added to a solution of 20 gm of the solid (2R-cis)-4-Amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidi- none.S-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate in water (200 ml) at 45-50 deg C. Stirred the reaction for 1 hour at room temperature. The solid S-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate was filtered and the aqueous layer was neutralized with aqueous sodium hydroxide solution (30%, 20 ml). The solvent was recovered under vacuum at 40-45 deg C., the product obtained was dissolved in methanol (200 ml), filtered to remove the inorganic salts, the filtrate was concentrated under vacuum at 40-45 deg C. and the residual solid obtained was dissolved in ethanol (50 ml), heated to 50 deg C., slowly allowed to room temperature, cooled to 10 deg C., filtered and dried at 40-45 deg C. to obtain 5 gm of Lamivudine(Chiral purity: 97.5%).
 | | Definition | ChEBI: Lamivudine is a monothioacetal that consists of cytosine having a (2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl moiety attached at position 1. An inhibitor of HIV-1 reverse transcriptase. | | Brand name | Epivir (GlaxoSmithKline). | | Acquired resistance | Long-term lamivudine administration frequently elicits viral resistance characterized by a reincrease of viral replication in an adherent patient. The incidence of lamivudine resistance is 14% to 32% after 1 year of treatment, 38% after 2 years, and 53% to 76% after 3 years. | | Pharmaceutical Applications | An analog of cytidine available for oral administration. | | Pharmacokinetics | The pharmacokinetics of lamivudine are similar in patients with HIV-1 or HBV infection, and healthy volunteers. The drug is rapidly absorbed after oral administration, with maximum serum concentrations usually attained 0.5 to 1.5 hours after the dose. | | Clinical Use | Lamivudine is indicated for the treatment of HIV when
used in combination with other antiretroviral agents.A
lower dose than that used to treat HIV is approved for
the treatment of HBV. | | Side effects | Lamivudine oral tablet can cause mild or serious side effects. The more common side effects that can occur with lamivudine include:
cough,diarrhea,fatigue,headache,malaise (general discomfort),nasal symptoms, such as a runny nose,nausea. | | Drug interactions | There are potentially dangerous interactions with other drugs when used in combination.
Antimicrobials: trimethoprim inhibits the excretion of lamivudine.
Antivirals: avoid concomitant use with foscarnet, emtricitabine, and IV ganciclovir
Cytotoxic drugs: avoid concomitant use with clarithromycin.
Orlistat: absorption may be reduced by orlistat. | | Metabolism | Lamivudine is metabolised intracellularly to the active antiviral triphosphate. Hepatic metabolism is low (5-10%) and the majority of lamivudine is excreted unchanged in the urine via glomerular filtration and active secretion (organic cationic transport system). | | References | Arts and Wainberg (1996), Mechanism of nucleoside analog antiviral activity and resistance during human immunodeficiency virus reverse transcription; Antimicrob. Agents Chemother., 40 527
Coates et al. (1992), (-)-2’-deoxy-3’-thiacytidine is a potent, highly selective inhibitor of human immunodeficiency virus type 1 and type 2 replication in vitro; Antimicrob. Agents Chemother., 36 733
Kong et al. (2022), Targeted P2X7/NLRP3 signaling pathway against inflammation, apoptosis, and pyroptosis of retinal endothelial cells in diabetic retinopathy; Cell Death Dis., 13 336
Rajukar et al. (2022), Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer; Cancer Discov., 2021 Online ahead of print |
| | Lamivudine Preparation Products And Raw materials |
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