Anti Infection Entecavir Pharmaceutical Intermediate Entecavir
Product Description
Product Details
| Product name |
Entecavir |
| Cas number |
142217-69-4 |
| Appearance |
White powder |
| MF |
C12H15N5O3 |
| MW |
295.3 |
Drugs that inhibit replication of hepatitis B virus
Entecavir hydrate, Entecavir monohydrate, the latest first-line drug against hepatitis B virus. Entecavir is a cyclovaleryl guanosine analogue. Phase II/III clinical studies have shown that oral administration of 0.5 mg per day can effectively inhibit HBV-DNA replication in adults. Phase III clinical studies have shown that increasing the dose to 1mg daily can inhibit HBV DNA replication in patients with YMDD variants. The incidence of drug resistance was 0 in initial treatment patients at 1 year, but 5.8% in patients with YMDD mutation at 1 year. China's SFDA has also approved for the treatment of chronic hepatitis B patients.
Application&Function
Action mechanism
It is a guanine nucleoside analogue and has an inhibitory effect on hepatitis B virus (HBV) polymerase. It can be phosphorylated into an active triphosphate, which has a half-life of 15 hours in the cell. By competing with deoxyguanosine triphosphate, the natural substrate of HBV polymerase, Entecavir triphosphate inhibits all three activities of viral polymerase (reverse transcriptase) : (1) initiation of HBV polymerase; (2) Formation of negative reverse transcription chain of pregenomic mRNA; (3) Synthesis of positive strand of HBV DNA. Inhibition Constant (Ki) of Entecavir triphosphate on HBV DNA polymerase
Antiviral activity
In human HepG2 cells infected with wild-type hepatitis B virus, the concentration required for 50% viral DNA synthesis (EC50) of Entecavistatin is 0.004μM. The median EC50 value of Entecavir against lamivudine-resistant virus strains (rtL180M,rtM204V) was 0.26μM (range 0.01 to 0.059μM), while Entecavir had no clinically relevant activity against human immunodeficiency type 1 (HIV) grown in cell culture (EC50 >10μM).
Long-term studies in North American marmots showed that oral administration of 0.5mg/kg of entecavir per week (equivalent to a human dose of 1.0mg) kept viral DNA at undetectable levels (viral DNA levels <200 copies /ml by PCR) in three of them for up to 3 years. In any animal treated with this drug for up to 3 years, no drug-resistant changes in HBV polymerase were observed.
pharmacokinetics
Absorption: After oral administration in healthy people, the product is rapidly absorbed, reaching peak concentration (Cmax) in 0.5 to 1.5 hours. The drug is administered once a day, and stable state can be reached after 6-10 days, and the cumulative amount is about twice.
Effects of food on oral absorption: Taking 0.5mg of the product orally with a standard high-fat or low-fat meal resulted in a slight delay in absorption (from 0.75 hours to 1.0-1.5 hours), a 44-46% reduction in Cmax, and an 18-20% reduction in area under the curve (AUC). Therefore, the product should be taken on an empty stomach (at least 2 hours before or after a meal).
The pharmacokinetic data showed that the apparent volume of distribution exceeded the total body fluid volume, indicating that the product was distributed in various tissues.
In vitro experiments showed that the binding rate of the product to human plasma protein was 13%.
Metabolism and elimination: After administration of 14C-labeled Entecavir in humans and rats, no oxidation or acetylation metabolites of this product were observed, but small amounts of phase II metabolites glucuronide conjugates and sulfuric acid conjugates were observed. Entecavir is not a substrate, inhibitor, or inducer of the cytochrome P450 (CYP450) enzyme system.
Specification
About US
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