title: [Chemical characteristics, mechanism of action and antiviral activity of darunavir].
abstract: Darunavir is the result of wide and in-depth investigation into HIV protease inhibitors (PIs). This drug is a nonpeptide PI, with a distinct chemical structure that, by conferring it drug with enhanced binding affinity and a slower dissociation rate, makes it more potent than the remaining PIs developed to date. Because of its pharmacokinetic characteristics, darunavir must be coadministered with low doses of ritonavir. Furthermore, these characteristics allow oral administration (preferably with meals), once-daily administration in non-resistant HIV strains, and a less complicated treatment regimen with improved convenience in highly varied contexts, including mild-to-moderate renal and hepatic impairment. The potential of darunavir for pharmacological interactions is highly acceptable and this drug can be administered without dose adjustments with almost all antiretroviral agents except maraviroc, lopinavir, saquinavir and tipranavir. There are no problems of pharmacodynamic antagonism with any of these drugs. Cytotoxic doses are well above therapeutic doses, providing a wide safety margin. The spectrum of action is very wide, and darunavir is effective against all subtypes of HIV-1 and against HIV-2 and acts well in mononuclear and monocyte/macrophage cell lines. Darunavir is also active against most HIV strains resistant to the remaining PIs and the robustness of this drug against the known mechanisms of resistance of HIV is also superior to that of the other available PIs. Consequently, the induction and selection of mutations conferring resistance to this drug may be slower and more difficult, resulting in its antiviral effect remaining unchanged for prolonged periods.
authors.affiliation: Unidad de Enfermedades Infecciosas. Hospital Virgen de las Nieves. Granada. España. jpasquau@nacom.es
authors.forename: Juan
authors.initials: J
authors.lastname: Pasquau Liaño
authors.forename: Carmen
authors.initials: C
authors.lastname: Hidalgo Tenorio
mesh_terms: D000284:Administration, Oral; D002219:Carbamates / Q000737:chemistry; D002986:Clinical Trials as Topic; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D000069454:Darunavir; D004347:Drug Interactions; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D006678:HIV / Q000187:drug effects* / Q000201:enzymology; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D015394:Molecular Structure; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D019438:Ritonavir; D000069454:Darunavir