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Doravirine API Manufacturers & Suppliers

General Description:

Doravirine, identified by CAS number 1338225-97-0, is a notable compound with significant therapeutic applications. Doravirine is an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) intended to be administered in combination with other antiretroviral medicines. Doravirine is available by itself or as a combination product of doravirine (100 mg), lamivudine (300 mg), and tenofovir disoproxil fumarate (300 mg). Doravirine is formally indicated for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment experience, further expanding the possibility and choice of therapeutic treatments available for the management of HIV-1 infection.

Indications:

This drug is primarily indicated for: Doravirine is indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment history. It is also indicated to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Doravirine undergoes metabolic processing primarily in: Following absorption, unchanged parent drug is the major circulating component in plasma. Its M9 metabolite - a product of cytochrome P450 3A4/5 mediated oxidative metabolism - is the most abundant doravirine metabolite in the circulation. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Doravirine are crucial for its therapeutic efficacy: The absolute bioavailability of doravirine is 64% with a T_max of 2 hours. Following oral doravirine administration, all of the administered dose was recovered and the agent is considered to be well absorbed. Moreover, its co-administration with food did not greatly alter doravirine's pharmacokinetic profile during clinical studies. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Doravirine is an important consideration for its dosing schedule: The elimination half-life determined of doravirine is 15 hours. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Doravirine exhibits a strong affinity for binding with plasma proteins: Doravirine is approximately 76% protein-bound in plasma. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Doravirine from the body primarily occurs through: The primary route of elimination for doravirine is via cytochrome P450 3A4/5 metabolism. Only 6% of an administered dose is recovered in the urine unchanged, with even less unchanged drug found in the feces. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Doravirine is distributed throughout the body with a volume of distribution of: The steady-state volume of distribution of doravirine following intravenous administration is 60.5 L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Doravirine is a critical factor in determining its safe and effective dosage: The oral and renal clearances of doravirine are 106 ml/min and 9.3 ml/min, respectively. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Doravirine exerts its therapeutic effects through: In a clinical phase 2 trial evaluating a dose range of 0.25-2x the recommended dose of doravirine (in combination with emtricitabine/tenofovir) in HIV-1 infected subjects with no antiretroviral treatment history, no exposure-response relationship for efficacy was identified for doravirine. Furthermore, at a dose of 1200 mg, which provides approximately 4 times the peak concentration observed following the recommended dose, doravirine does not prolong the QT interval to any clinically relevant extent. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Doravirine functions by: Doravirine is a pyridinone non-nucleoside reverse transcriptase inhibitor of HIV-1. Reverse transcriptase is the enzyme with which HIV generates complementary DNA (cDNA) to its RNA genome - this cDNA is then inserted into the host cell genome, where it can be transcribed into viral RNA for the purposes of replication. Doravirine inhibits HIV-1 replication by non-competitively inhibiting HIV-1 reverse transcriptase. Doravirine does not, however, inhibit the human cellular DNA polymerases α, ß, and mitochondrial DNA polymerase γ. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Doravirine belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups, classified under the direct parent group Diarylethers. This compound is a part of the Organic compounds, falling under the Organic oxygen compounds superclass, and categorized within the Organooxygen compounds class, specifically within the Ethers subclass.

Categories:

Doravirine is categorized under the following therapeutic classes: Antiinfectives for Systemic Use, Antiviral Agents, Antivirals for Systemic Use, Antivirals used in combination for the treatment of HIV infections, Cytochrome P-450 CYP3A Substrates, Cytochrome P-450 CYP3A4 Substrates, Cytochrome P-450 CYP3A5 Substrates, Cytochrome P-450 Substrates, Direct Acting Antivirals, Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor, Non-Nucleoside Reverse Transcriptase Inhibitors, Nonnucleoside Reverse Transcriptase Inhibitors, Pyridines. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.