Darunavir

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Cat Number

API0232241

CAS Number

206361-99-1

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CAS Number

206361-99-1

EINECS

606-590-1

Storage

Store at room temperature

Synonyms

TMC-114; UIC-94017; Darunavirum; (-)-DARUNAVIR; DTXSID0046779

Molecular Formula

C27H37N3O7S

Molecular Weight

547.7

Smiles

CC(C)CN(C[C@H]([C@H](CC1=CC=CC=C1)NC(=O)O[C@H]2CO[C@@H]3[C@H]2CCO3)O)S(=O)(=O)C4=CC=C(C=C4)N

Appearance

White to off-white powder

Melting Point

74-76°C

Relative Density

1.34±0.1 (Predicted)

General Description

Darunavir is a synthetic nonpeptidic HIV protease inhibitor with a bis-tetrahydrofuranylurethane (bis-THF) core, which enhances its binding affinity. Its chemical structure is (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-[(1S,2R)-1-benzyl-2-hydroxy-3-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]propyl]carbamate.

Mechanism of Action

Darunavir binds selectively to the HIV-1 protease enzyme, inhibiting its activity and preventing the cleavage of the viral polyprotein precursor. This blocks the maturation of the virus, leading to the production of non-infectious viral particles. The drug has a high genetic barrier to resistance, requiring multiple mutations for loss of activity, and it is effective against many protease inhibitor-resistant strains.

Application

Darunavir is indicated for the treatment of HIV-1 infection in combination with ritonavir and other antiretroviral agents, in both treatment-naïve and treatment-experienced patients. It is effective in reducing viral load and increasing CD4 cell count.

A physiologically based pharmacokinetic (PBPK) model for darunavir/ritonavir that included hepatic uptake/efflux transporters and enterohepatic circulation accurately predicted darunavir exposure, whereas a well‑stirred liver model overestimated it. The model approximated the decrease in darunavir AUC during pregnancy (27–41% predicted vs 17–33% observed). Hepatic transporters play a clinically relevant role, and the model supports their inclusion to guide dosing in pregnancy.

Fig. 1 Rate of darunavir disappearance (V) from human liver microsomal incubations at increasing substrate concentrations. (Colbers A, et al., 2016)

References

Colbers A, et al. Physiologically Based Modelling of Darunavir/Ritonavir Pharmacokinetics During Pregnancy. Clin Pharmacokinet. 2016;55(3):381-396.

In the D²EFT trial (828 participants, 14 countries), three second-line ART strategies after NNRTI failure were compared. Virological suppression (<50 copies/mL) at 48 weeks was 75% for ritonavir-boosted darunavir + 2 NRTIs (standard), 84% for darunavir/ritonavir + dolutegravir, and 78% for dolutegravir + tenofovir/lamivudine or emtricitabine. The darunavir/ritonavir + dolutegravir arm showed significantly better suppression (difference 8.6%, p=0.016). No treatment-related deaths or congenital defects occurred. Dolutegravir-containing regimens are effective second-line options.

Fig. 2 Consort diagram for all participants screened to randomisation. (D2EFT Study Group. 2024)

References

D2EFT Study Group. Dolutegravir plus boosted darunavir versus recommended standard-of-care antiretroviral regimens in people with HIV-1 for whom recommended first-line non-nucleoside reverse transcriptase inhibitor therapy has failed (D2EFT): an open-label, randomised, phase 3b/4 trial. Lancet HIV. 2024;11(7):e436-e448.

Does Darunavir require protection from moisture during long-term storage?

Yes, it is slightly hygroscopic and susceptible to hydrolysis of the sulfonamide and carbamate groups. Store in tightly sealed containers with desiccant.

What is the recommended storage temperature for Darunavir?

Store at controlled room temperature (15-25°C). Avoid temperatures above 30°C, which accelerate degradation and formation of the despyridone impurity.

Is Darunavir stable in tablet formulations with standard excipients?

Yes, when formulated with moisture-protective packaging (e.g., HDPE bottles with desiccant).

How is the impurity darunavir despyridone (a hydrolysis product) monitored?

This primary degradation product is specifically quantified using a stability-indicating HPLC method, ensuring it remains within ICH limits.