GMP Certified / Tenofovir Alafenamide Fumarate Tablets

• Quality Standard: Bp, USP
• Ctd Dossier: Ready
• Documentation: Copp, COA
• Factory Certification: GMP
• Transport Package: Carton
• Specification: 25mg
• Model NO.: Tablet
• Trademark: Sinolead
• Origin: China
• Production Capacity: 100, 000, 000 Per Year

Product Description

Product Description

Generic Name	Tenofovir Alafenamide Fumarate tablets
Strength	25 mg
Packing	30 tablets /bottle
Origin	China

Value-added services:
 Packaging design by our team
 Registration service by our team
 Registration dossier available by our team
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Product name:
Tenofovir Alafenamide Fumarate tablets

Character:
This product is yellow, round film coating. After the coating is removed, it appears white or near-white. The tablet is 8mm in diameter and has "GSI" inscribed on one side and "25" inscribed on the other.

Indications:
The drug is used to treat chronic liver B (HBV) in adults and adolescents (over 12 years of age and weighing at least 35kg).


Pharmacology and toxicology:
Pharmacological action
Action mechanism
Tenofovir profol is a phosphite drug precursor of Tenofovir (2' -deoxyadenosine monophosphate analogue).
Pofotenofovir enters primary hepatocytes via passive diffusion and liver uptake transporters OATP1B1 and OATP1B3. Tenofovir profol was hydrolyzed by carboxylesterase 1 to form tenofovir in primary hepatocytes. Cellular tenofovir is subsequently phosphorylated to form the pharmacologically active metabolite Tenofovir diphosphate. Tenofovir diphosphate is incorporated into viral DNA by HBV reverse transcriptase integration (which results in the termination of the DNA strand), thereby inhibiting HBV replication.
Tenofovir has specific activity against hepatitis B virus and human immunodeficiency virus (HIV-1 and HIV-2). Based on several studies, including mitochondrial DNA analysis, tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases, including mitochondrial DNA polymerase γ, with no signs of mitochondrial toxicity in vitro.
Antiviral activity
The antiviral activity of profotenofovir against A set of HBV clinical isolates representing genotype A-H was evaluated in HepG2 cells. The EC50 (50% effective concentration) value of Tenofovir profol ranges from 34.7 to 134.4 nM, with an overall mean EC50 of 86.6 nM. CC50 (50% cytotoxic concentration) in HepG2 cells was > 44400 nM.
Drug resistance
In a pooled analysis of overseas patients treated with pofol and tenofovir fumarate tablets, HBV DNA ≥ 69 IU/mL at 2 consecutive follow-up visits was targeted for a virological breakthrough (HBV DNA < 69 IU/mL). Or an increase of 1.0 log10 or more relative to the minimum HBVDNA), patients with HBVDNA ≥ 69IU/mL (week 96 only), or patients with HBVDNA ≥ 69IU/mL at early withdrawal at week 24 or later, Sequence analysis of paired baseline and treatment HBV isolates was performed. At week 48 (N=20) and week 96 (N=72) analyses of overseas patients, amino acid substitution associated with resistance to Pofol tenofovir fumarate tablets was not identified in these isolates (genotype and phenotypic analysis).
Cross resistance
The antiviral activity of tenofovir profol against a group of nucleoside (acid) reverse transcriptase inhibitor mutated isolates was evaluated in HepG2 cells. HBV isolates that expressed rtV173L, rtL180M, and rtM204V/I substitutions associated with lamivudine resistance were still sensitive to tenofovir profol (EC50 change factor < 2). HBV isolates that expressed rtL180M, rtM204V + rtT184G, rtS202G or rtM250V substitutions associated with entecavir resistance remained sensitive to tenofovir profol. HBV isolates expressing single mutations of rtA181T, rtA181V or rtN236T associated with adefovir resistance were still sensitive to tenofovir profol. However, HBV isolates expressing rtA181V + rtN236T showed reduced sensitivity to tenofovir profol (EC50 change factor 3.7). The clinical relevance of these substitutions is unclear.
Non-clinical toxicology
Non-clinical studies in rats and dogs have shown that bones and kidneys are the main target organs for toxicity. BMD was observed to reduce this skeletal toxicity in rats and dogs when tenofovir exposure was at least four times the amount expected after tenofovir profol administration. At exposure to tenofovir and tenofovir about 4 and 17 times the expected exposure after administration of tenofovir, respectively, a very slight histiocytic infiltration occurred in the eyes of dogs.
Tenofovir profol did not cause mutagenicity or chromosome breakage in conventional genotoxicity analysis.
Compared to Tenofovir fumarate, tenofovir exposure to profol was lower in rats and mice after administration, so only Tenofovir fumarate was used in carcinogenicity studies and perinatal - postnatal studies in rats. Routine studies of carcinogenicity with tenofovir dipivoxil (fumarate form) and routine studies of reproduction and development with Tenofovir dipivoxil (fumarate form) or tenofovir profol have shown no particular harm to humans. Reproductive toxicity studies in rats and rabbits have shown no effect on mating, fertility, pregnancy, or fetal parameters. However, in perinatal-postnatal toxicity studies at maternal toxic doses, tenofovir fumarate reduced vigour index and body weight in the pups. Long-term studies of the carcinogenicity of oral administration in mice have shown a lower incidence of duodenal tumors, which is thought to be possibly related to higher local concentrations of gastrointestinal drugs at higher doses of 600 mg/kg/ day. The mechanism of tumor formation in mice and its potential relevance in humans have not been determined.


Storage:
Store below 30°C.