Tenofovir disoproxil

Description

Tenofovir disoproxil belongs to a class of medications called antiretroviral known as a nucleotide reverse transcriptase inhibitor, which is commonly used to treat the infection caused by the human immunodeficiency virus (HIV) generally in combination with other antiviral agents. It can also be used for prevention of HIV/AIDS among those people who are at high risk before exposure, such as injection through sexual transmission or injection of drugs. It functions by blocking reverse transcriptase, an enzyme vital to viral duplication in people infected HIV. Besides, it is effective to treat chronic hepatitis B, in which it helps prevent the enzymes needed for the hepatitis B virus to reproduce from working properly. However, tenofovir disoproxil does not cure HIV/AIDS or hepatitis B. It helps lower the amount of HIV or hepatitis B virus in the body and slow down the progression of the disease. Tenofovir was patented in 1996 and approved for use in the United States in 2001.

References

https://en.wikipedia.org/wiki/Tenofovir_disoproxil
http://bodyandhealth.canada.com/drug/getdrug/viread
https://www.drugbank.ca/drugs/DB00300

Description

Tenofovir disoproxil is a prodrug in a manner similar to that of adefovir dipivoxil. In both cases, the phosphate esters are removed through the action of plasma esterase, leading in this case to tenofovir, which differs from adefovir by the presence of the indicated methyl group. Tenofovir disoproxil exhibits good bioavailability (25%), which is improved in the presence of food (35%). The drug is approved for the treatment of HIV infections in adult patients. Tenofovir diphosphate is an HIV RT inhibitor. The active form of tenofovir is the tenofovir diphosphate, which competes with dATP for incorporation into viral DNA, and when incorporated, tenofovir diphosphate results in premature termination of DNA growth and inhibition of DNA polymerase. Tenofovir disoproxil is indicated for treatment-experienced patients with HIV-1. The drug also appears to be effective in treatment-naive patients, but initial approval is for treatment-experienced patients. The drug is administered as one tablet taken once daily. It is recommended that the drug be combined with other RT inhibitors or HIV PIs, which results in additive or synergistic activity.

Uses

Tenofovir Disoproxil is a therapeutic option for nucleos(t)ide analog (NA)-experienced chronic hepatitis B (CHB) patients infected with hepatitis B virus (HBV). Also, it is an intermediate used in the synthesis of Tenofovir Disoproxil Dimer (T018515), which is a Tenofovir Disoproxil impurity.

Definition

ChEBI: An organic phosphonate that is the disoproxil ester of tenofovir. A prodrug for tenofovir, an HIV-1 reverse transcriptase inhibitor, tenofovir disoproxil is used as the fumaric acid salt in combination therapy for the treatment of HIV infection.

General Description

Tenofovir disoproxil is a prodrug analogously with abacavir.Plasma and tissue esterases cleave the phosphateprotecting groups, releasing the active drug. The bioavailabilityof tenofovir is about 35% when administered withfood. The drug is approved by the Food and DrugAdministration (FDA) for the treatment of HIV infectionsin adult patients. Recommendations are for the drug to beadministered with other RT inhibitors or PIs to achievesynergism.

Clinical Use

Nucleoside reverse transcriptase inhibitor:
Treatment of HIV in combination with other antiretroviral drugs
Treatment of hepatitis B in compensated liver disease

Drug interactions

Potentially hazardous interactions with other drugs
Antivirals: avoid with adefovir and cidofovir; reduces concentration of atazanavir, also concentration of tenofovir possibly increased; increased didanosine concentration resulting in increased toxicity (e.g. pancreatitis and lactic acidosis) - avoid; concentration increased by lopinavir and telaprevir.
Co-administration with other drugs that are actively secreted via the tubular anionic transporter.
Orlistat: absorption possibly reduced by orlistat.

Metabolism

Tenofovir is excreted mainly in the urine by both active tubular secretion and glomerular filtration.