title: Cobicistat: a review of its use as a pharmacokinetic enhancer of atazanavir and darunavir in patients with HIV-1 infection.
abstract: Cobicistat (Tybost™) is a mechanism-based inhibitor of cytochrome P450 (CYP) 3A enzymes that is indicated in the EU as a pharmacokinetic enhancer (i.e. booster) of the HIV-1 protease inhibitors (PIs) atazanavir and darunavir in adults. Cobicistat has a lower potential for off-target drug interactions than the standard boosting agent ritonavir, due to its more selective inhibition of CYP3A and lower likelihood for enzymatic induction, and is devoid of anti-HIV activity. When used to boost darunavir or atazanavir in healthy volunteers, oral cobicistat 150 mg once daily provided bioequivalent PI exposure to that seen with oral ritonavir 100 mg once daily (i.e. low-dose ritonavir). Moreover, in treatment-naïve adults infected with HIV-1 participating in a large, double-blind, phase III trial, an atazanavir-based antiretroviral regimen boosted with cobicistat 150 mg once daily provided a high rate of virological suppression after 48 weeks of therapy that was noninferior to that seen with low-dose ritonavir boosting. Cobicistat was generally well tolerated in this study, with a tolerability profile similar to that of ritonavir. Cobicistat may increase serum creatinine levels (possibly via inhibition of proximal renal tubular cell transporters) and thus reduce estimated glomerular filtration rate (GFR), although it does not appear to affect actual GFR. The drug is more soluble than ritonavir, making coformulation easier, and fixed-dose formulations combining cobicistat with darunavir and atazanavir are in development. Thus, cobicistat is an emerging alternative to ritonavir for the pharmacokinetic enhancement of PIs in adults with HIV-1 infection.
authors.affiliation: Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand, demail@springer.com.
authors.forename: Emma D
authors.initials: ED
authors.lastname: Deeks
mesh_terms: D000069446:Atazanavir Sulfate; D002219:Carbamates / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000069547:Cobicistat; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000069454:Darunavir; D004357:Drug Synergism; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D009842:Oligopeptides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011725:Pyridines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013449:Sulfonamides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013844:Thiazoles / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002219:Carbamates; D065692:Cytochrome P-450 CYP3A Inhibitors; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D013449:Sulfonamides; D013844:Thiazoles; D000069446:Atazanavir Sulfate; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D000069547:Cobicistat; D000069454:Darunavir