title: [Mechanisms of action, pharmacology and interactions of dolutegravir].
abstract: Dolutegravir is a second-generation integrase strand transfer inhibitor (INSTI), whose potential and binding half-life in the integrase are far superior to those of raltegravir and elvitegravir, conferring it with unique characteristics in terms of its genetic barrier to resistance and activity against viruses with one or more mutations in the integrase. The pharmacokinetic properties of dolutegravir allow once-daily dosing (50 mg), with or without food, maintaining concentrations far above those effective against wild-type viruses. If integrase resistance mutations are present, the recommended dosing regimen is 50 mg/12 h. The distribution of dolutegravir in cerebrospinal fluid is good and effective concentrations are also reached in the male and female genital tracts. Dolutegravir is metabolized by UGT1A1 and, to a lesser extent, by CYP3A4, without being an inducer or inhibitor of the usual metabolic systems. It has a very low potential for drug interactions and can be administered in routine doses with most drugs. Dose adjustment is not required, even in patients with renal insufficiency or mild or moderate liver failure. Increasing the dose of dolutegravir (50 mg/12 h) is only recommended when administered with efavirenz, nevirapine, fosamprenavir/r, tipranavir/r, rifampicin, carbamazepine, phenytoin and phenobarbital. Coadministration of dolutegravir with etravirine is not recommended without a protease inhibitor or with Hypericum perforatum. Dolutegravir should be administered 2 h before or 6 h after antacids or products with polyvalent cations. Dolutegravir can reduce renal tubule secretion of substances excreted via OCT2, with a slight initial increase in creatinine, with no risk of renal toxicity. The drug can also increase metformin concentrations and consequently monitoring is recommended in case dose adjustment is required. In summary, dolutegravir has excellent pharmacokinetic and drug interaction profiles.
authors: Servicio de Enfermedades Infecciosas, Hospital Universitario Vall d'Hebron, Barcelona, España. Electronic address: eriberap@gmail.com.
authors: Esteban
authors: E
authors: Ribera
authors: Servicio de Enfermedades Infecciosas, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, España.
authors: Daniel
authors: D
authors: Podzamczer
mesh_terms: D000863:Antacids / Q000493:pharmacokinetics; D000890:Anti-Infective Agents / Q000493:pharmacokinetics; D000927:Anticonvulsants / Q000493:pharmacokinetics; D001711:Biotransformation; D002413:Cations, Divalent / Q000493:pharmacokinetics; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy; D019428:HIV Integrase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006575:Heterocyclic Compounds, 3-Ring / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D015394:Molecular Structure; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D016662:Virus Integration / Q000187:drug effects; D000099148:UGT1A1 Enzyme; D000099226:Dolutegravir
chemical_list: D000863:Antacids; D000890:Anti-Infective Agents; D000927:Anticonvulsants; D002413:Cations, Divalent; D051544:Cytochrome P-450 CYP3A; D014453:Glucuronosyltransferase; D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D000099148:UGT1A1 Enzyme; D000099226:Dolutegravir; C510163:CYP3A4 protein, human
keywords: Dolutegravir; Farmacocinética; Farmacología; Human immunodeficiency virus; Inhibidores de la integrasa; Integrase inhibitors; Interacciones; Interactions; Pharmacokinetics; Pharmacology; Virus de la inmunodeficiencia humana