Abstract:
UNLABELLED:Darunavir is an oral nonpeptidic HIV-1 protease inhibitor (PI) that is used, together with a low boosting dose of ritonavir, as part of an antiretroviral therapy (ART) regimen in treatment-experienced and -naive patients with HIV-1 infection. Compared with early-generation PIs, boosted darunavir has a high genetic barrier to resistance and is active against multidrug-resistant HIV isolates. In clinical trials in treatment-experienced patients with HIV-1 infection receiving an optimized background regimen (OBR), twice-daily boosted darunavir was more effective than investigator-selected ritonavir-boosted control PIs (CPIs) or ritonavir-boosted lopinavir. In clinical trials in treatment-naive patients with HIV-1 infection receiving a fixed background regimen, once-daily boosted darunavir was noninferior to boosted lopinavir at 48 weeks and more effective than boosted lopinavir at 96weeks. Boosted darunavir was generally well tolerated in patients with HIV-1 infection in clinical trials. It was associated with a lower incidence of diarrhoea than CPIs or lopinavir in treatment-experienced or -naive patients, and fewer lipid abnormalities than lopinavir in treatment-naive patients. Thus, for the management of treatment-experienced or -naive patients with HIV-1 infection, a ritonavir-boosted darunavir-based ART regimen is a valuable treatment option. PHARMACOLOGICAL PROPERTIES: Darunavir is an oral nonpeptidic HIV-1 PI that selectively inhibits the cleavage of HIV gag and gag-pol polyproteins, thereby preventing viral maturation. Darunavir is highly potent against laboratory strains and clinical isolates of wild-type and multidrug-resistant HIV and has limited cytotoxicity. In an in vitro study in MT-2 cells, the potency of darunavir was greater than that of saquinavir, amprenavir, nelfinavir, indinavir, lopinavir and ritonavir. Darunavir binds with high affinity to HIV-1 protease, including multidrug-resistant proteases, and retains potency against multidrug-resistant HIV-1 strains. Although some potential may exist for cross-resistance with amprenavir, darunavir did not display cross-resistance with other PIs in vitro. In a 24-week analysis of pooled data from the POWER 1 and 2 studies in treatment-experienced patients, 11 protease mutations associated with a reduced response to boosted darunavir were identified (V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V and L89V). The presence of at least three darunavir resistance-associated mutations (prevalent in approximately 7-9% of treatment-experienced patients) together with a high number of protease resistance-associated mutations were required to confer darunavir resistance. In the 48-week analysis of treatment-experienced patients with virological failure in the the TITAN study, fewer in the boosted darunavir group than in the boosted lopinavir group developed additional mutations or lost susceptibility to PIs compared with baseline. In treatment-naive patients, no primary PI-resistance-associated mutations developed in patients with an available genotype at baseline and endpoint during 96 weeks of treatment with boosted darunavir or boosted lopinavir. Oral darunavir, boosted with low-dose ritonavir, is rapidly absorbed, generally reaching peak plasma concentrations within 2.5-4 hours. The bioavailability of oral darunavir is increased by about 30% when taken with food. Darunavir is primarily metabolized by the hepatic cytochrome P450 (CYP) enzymes, primarily CYP3A. The 'boosting' dose of ritonavir acts an an inhibitor of CYP3A, thereby increasing darunavir bioavailability. Drug interactions can result when darunavir is coadministered with other drugs that are inducers or inhibitors of, or act as substrates for, CYP3A. The mean elimination half-life of boosted darunavir is approximately 15 hours. THERAPEUTIC EFFICACY: In treatment-experienced patients with HIV-1 infection, the therapeutic efficacy of oral twice-daily darunavir 600 mg, boosted with ritonavir 100 mg, versus that of investigator selected boosted CPIs (POWER studies) or versus twice-daily boosted lopinavir (administered as a fixed dose combination of lopinavir/ritonavir 400/100 mg) [TITAN study] has been evaluated in phase IIb and III studies. All patients received concurrent treatment with an OBR. Significantly more patients receiving boosted darunavir achieved a viral load reduction from baseline of >or=1 log(10) copies/mL (primary endpoint) than boosted CPI recipients at all timepoints, up to and including the final efficacy analysis at 144 weeks, in the combined analyses of POWER 1 and 2. The efficacy of boosted darunavir was noninferior to that of boosted lopinavir at 48 weeks, and was significantly better than boosted lopinavir at 48 and 96 weeks in the TITAN study, as determined by significantly more patients in the darunavir group than in the lopinavir group achieving a viral load of <400 copies/mL (primary endpoint). In the ARTEMIS study in treatment-naive patients with HIV-1 infection receiving a fixed background regimen of tenofovir and emtricitabine, once-daily boosted darunavir 800 mg was noninferior to boosted lopinavir 800 mg/day at 48 weeks. At 96 weeks, boosted darunavir was found to be more effective than boosted lopinavir, as determined by significantly more patients in the darunavir group than in the lopinavir group achieving a confirmed plasma viral load of <50 copies/mL (primary endpoint). TOLERABILITY:Boosted darunavir was generally well tolerated in patients with HIV-1 infection in clinical trials, with most events being mild to moderate in severity. At 48-week analyses, the most common adverse events associated with once- or twice-daily boosted darunavir in treatment-experienced or -naive patients were diarrhoea, nausea, headache, upper respiratory tract infection and nasopharyngitis. The most common boosted darunavir-related grade 2-4 laboratory abnormalities in treatment-experienced patients included increased triglycerides and increased total cholesterol. Overall, boosted darunavir was associated with less diarrhoea than CPIs or boosted lopinavir in treatment-experienced and -naive patients, and a lower incidence of grade 2-4 elevations in triglycerides and total cholesterol than boosted lopinavir in treatment-naive patients. Treatment discontinuation because of adverse events occurred in 3% of boosted darunavir recipients and 7% of boosted lopinavir recipients during 48 weeks of therapy in treatment-naive patients. PHARMACOECONOMIC CONSIDERATIONS: Healthcare costs in the UK and US were estimated to be lower with boosted darunavir than with investigator-selected CPIs in treatment-experienced patients with HIV-1 infection in two 1-year cost analyses conducted from the perspective of a healthcare provider and using predicted costs based on CD4+ cell counts and clinical data from the POWER studies. The higher acquisition cost of boosted darunavir compared with CPIs was more than offset by the better efficacy of darunavir. In modelled cost-effectiveness analyses, boosted darunavir was predicted to be cost effective compared with other boosted CPIs in heavily pretreated adults from a healthcare payer perspective in Europe and from a societal perspective in the US. In a further model of a subgroup of patients with at least one primary International AIDS Society-USA PI mutation, boosted darunavir was predicted to be cost effective compared with boosted lopinavir from a healthcare payer perspective in Europe. The incremental costs per quality-adjusted life-year gained were within commonly accepted thresholds in all cost-effectiveness analyses.
journal_name
Drugsjournal_title
Drugsauthors
McKeage K,Perry CM,Keam SJdoi
10.2165/00003495-200969040-00007subject
Has Abstractpub_date
2009-01-01 00:00:00pages
477-503issue
4eissn
0012-6667issn
1179-1950pii
7journal_volume
69pub_type
杂志文章,评审相关文献
DRUGS文献大全abstract::Tuberous sclerosis complex (TSC) is a genetic disorder arising from mutations in the TSC1 or TSC2 genes. The resulting over-activation of the mammalian target of rapamycin (mTOR) signalling pathway leaves patients with TSC susceptible to the growth of non-malignant tumours in multiple organs. Previously, surgery was t...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.1007/s40265-016-0552-9
更新日期:2016-04-01 00:00:00
abstract::The disposition of many drugs in cystic fibrosis is abnormal. In general, changes in pharmacokinetics include: increased volume of distribution, decreased plasma concentration, and enhanced renal and sometimes non-renal elimination of drugs. Pathophysiology of the disease important for drug disposition includes: (a) h...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-198835050-00004
更新日期:1988-05-01 00:00:00
abstract::Hepatitis C virus (HCV) infection is associated with a variable disease course and response to therapy. Some infected patients may develop little or no disease for 30 to 40 years, whereas others will develop cirrhosis within 5 to 10 years. Both host and viral factors influence the rate of disease progression. The mana...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-199600522-00003
更新日期:1996-01-01 00:00:00
abstract::Porcine-derived lung surfactant (PLS; Curosurf) has shown efficacy in neonatal respiratory distress syndrome. PLS consists of phospholipids, mainly dipalmitoylphosphatidylcholine, the primary surface-active agent of natural lung surfactant, and pulmonary surfactant-associated proteins which facilitate spreading and ad...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-199448030-00006
更新日期:1994-09-01 00:00:00
abstract::This paper reviews the evidence that, in patients with hypertension, end-organ damage correlates more closely with blood pressure values obtained by ambulatory blood pressure monitoring than with those obtained by conventional sphygmomanometry. However, ambulatory blood pressure monitoring is not suitable for routine ...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-199200441-00004
更新日期:1992-01-01 00:00:00
abstract::Alterations of skin and hair pigmentation are important features that have warranted treatment from ancient history on up to modern time. In some cultures, even today patients with vitiligo are regarded as social outcasts and are affected considerably both emotionally and physically. This article presents current opti...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-200464010-00006
更新日期:2004-01-01 00:00:00
abstract::Arrhythmia treatment has always been difficult, particularly as there are no good indicators of the optimal management strategy. The introduction of new antiarrhythmic agents has forced reappraisal of how these drugs are used. Dynamic electrocardiography and invasive electrophysiological studies are important tools fo...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-198836050-00005
更新日期:1988-11-01 00:00:00
abstract::Lapatinib (Tyverb, Tykerb) is an orally active, small molecule, reversible, dual tyrosine kinase inhibitor of human epidermal growth factor receptor type 1 (HER1) and type 2 (HER2). In the EU, lapatinib in combination with capecitabine is indicated for the treatment of women with HER2-overexpressing, advanced or metas...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/11203240-000000000-00000
更新日期:2009-10-22 00:00:00
abstract::Knowledge of the structure, function and distribution of the components of the renin-angiotensin-aldosterone system (RAS) and the integrated physiological role of this hormonal system is rapidly increasing, although many questions remain unanswered. The primary structure and localisation of RAS such as renin, prorenin...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-199000391-00005
更新日期:1990-01-01 00:00:00
abstract::Emicizumab (Hemlibra®), a recombinant, humanized, bispecific monoclonal antibody, restores the function of missing activated factor VIII (FVIII) by bridging FIXa and FX to facilitate effective haemostasis in patients with haemophilia A. Subcutaneous emicizumab is approved in several countries, including in the USA and...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.1007/s40265-019-01200-2
更新日期:2019-10-01 00:00:00
abstract::HMG-CoA reductase inhibitors (statins) have been shown to reduce mortality and cardiovascular morbidity in patients with hyperlipidaemia and those with coronary artery disease. However, evidence for statin treatment in patients with chronic heart failure (CHF) remains a subject of debate. Patients with heart failure w...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-200666020-00002
更新日期:2006-01-01 00:00:00
abstract::Cenegermin (Oxervate™), an ophthalmic solution containing 20 µg/mL of recombinant human nerve growth factor (rhNGF), is the first drug to be approved for the treatment of neurotrophic keratitis (NK; also referred to as neurotrophic keratopathy). In the registration trials, the majority of adults with moderate or sever...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.1007/s40265-020-01289-w
更新日期:2020-04-01 00:00:00
abstract::Dementia is commonly diagnosed at a time of major domestic breakdown, when symptoms are severe and family and community patience has been eroded. In order to encourage early referral and identification of patients with treatable conditions, a Memory Clinic is held at the University Hospital in Cardiff. The clinic prov...
journal_title:Drugs
pub_type: 杂志文章
doi:10.2165/00003495-198700332-00016
更新日期:1987-01-01 00:00:00
abstract::Terfenadine is a selective histamine H1-receptor antagonist which, in pharmacodynamic studies, is devoid of central nervous system depressant activity. In clinical studies terfenadine is well tolerated and at a dose of 60mg administered twice daily the drug provides effective relief of symptoms in patients with allerg...
journal_title:Drugs
pub_type: 临床试验,杂志文章,评审
doi:10.2165/00003495-199039040-00006
更新日期:1990-04-01 00:00:00
abstract::Eravacycline (Xerava™), a novel fully synthetic fluorocycline, consists of the tetracyclic core scaffold with unique modifications in the tetracyclic D ring; consequently, it exhibits potent in vitro activity against Gram-positive and -negative bacterial strains expressing certain common tetracycline-specific acquired...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.1007/s40265-019-01067-3
更新日期:2019-02-01 00:00:00
abstract::Losartan/hydrochlorothiazide (HCTZ) [Hyzaar(R)] is a fixed-dose combination of the angiotensin II receptor antagonist (angiotensin receptor blocker [ARB]) losartan and the thiazide diuretic HCTZ. It is indicated for the treatment of hypertension (including as initial therapy in severe hypertension) and for stroke risk...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-200969090-00008
更新日期:2009-06-18 00:00:00
abstract::The annual incidence of skin and soft tissue infections (SSTIs) has nearly tripled in the US since the early 1990s. Many purulent SSTIs in the community setting are caused by methicillin-resistant Staphylococcus aureus (MRSA). Incision and drainage (I&D) are indicated for most purulent MRSA infections; however, the us...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/11599510-000000000-00000
更新日期:2012-02-12 00:00:00
abstract::Drug treatment for various anorectal conditions has been known since ancient times. Today, modern as well as traditional drugs are being increasingly used in all grades of symptomatic haemorrhoids. These drugs (oral and local) are used as a part of conservative management or as an adjuvant to invasive outpatient proce...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-200565110-00003
更新日期:2005-01-01 00:00:00
abstract::For almost half a century, the first-line treatment for ovulation induction in cases of anovulation, unexplained infertility, or mild male factor has been clomifene (clomiphene citrate). Clomifene is an effective and safely used oral agent, but is known to have relatively common antiestrogenic endometrial and cervical...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-200666170-00001
更新日期:2006-01-01 00:00:00
abstract::Despite advances in the understanding of the mechanism of cerebral injury during focal ischaemia, the best treatment of cerebral ischaemia is still prevention. The pathophysiological mechanisms that contribute to cerebral ischaemia are discussed relative to the many therapeutic interventions that have been attempted. ...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-198835040-00005
更新日期:1988-04-01 00:00:00
abstract::In the past 2 decades, progressive improvements in the results of organ transplantation as a therapeutic strategy for patients with end-stage organ disease have been achieved due to greater insight into the immunobiology of graft rejection and better measures for surgical and medical management. It is now known that T...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-199754040-00003
更新日期:1997-10-01 00:00:00
abstract::Echinocandins are a new class of antifungal agents with a novel mechanism of action (interference with fungal cell wall synthesis). Caspofungin (Cancidas), Caspofungin MSD) is the first echinocandin to be approved and is administered intravenously. Caspofungin 50 mg/day had similar efficacy to intravenous fluconazole ...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-200363200-00008
更新日期:2003-01-01 00:00:00
abstract::The efficacy and safety of cefadroxil in the treatment of paediatric patients with a wide variety of infections were evaluated in a multicentre clinical trial. This study included 395 infants and children with Group A streptococcal pharyngitis, sinusitis, otitis media, bronchitis, pneumonia or bronchopneumonia, urinar...
journal_title:Drugs
pub_type: 杂志文章
doi:10.2165/00003495-198600323-00005
更新日期:1986-01-01 00:00:00
abstract::Glucocorticoids are used for a variety of illnesses. One of their major complications is suppression of the hypothalamic-pituitary-adrenal axis, rendering a patient unable to respond to stress. The risk of this suppression may be minimised by the use of short-acting glucocorticoid preparations, administration of the e...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-198938050-00008
更新日期:1989-11-01 00:00:00
abstract::Oral fidaxomicin (Dificid(®); Dificlir(®)) is a first-in-class macrocyclic antibacterial that is approved in several countries for the treatment of adult patients with Clostridium difficile-associated diarrhoea. Fidaxomicin 200 mg twice daily for 10 days was an effective and generally well tolerated treatment in adult...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.1007/s40265-013-0134-z
更新日期:2013-10-01 00:00:00
abstract::Everolimus is an immunosuppressant that blocks growth factor-mediated proliferation of haematopoietic and nonhaematopoietic cells. Oral everolimus 0.75 or 1.5mg twice daily significantly reduced the incidence of the primary composite endpoint, efficacy failure 6 months after transplantation, compared with azathioprine...
journal_title:Drugs
pub_type: 杂志文章
doi:10.2165/00003495-200464080-00005
更新日期:2004-01-01 00:00:00
abstract::Damoctocog alfa pegol (Jivi®) is approved in the USA, EU, Japan and Canada for the treatment and prophylaxis of previously treated patients aged ≥ 12 years with haemophilia A. Formulated with a 60 kDa polyethylene glycol (PEG) moiety, damoctocog alfa pegol is an intravenously (IV) administered recombinant factor VIII ...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.1007/s40265-019-01152-7
更新日期:2019-07-01 00:00:00
abstract::Patients with oncogene-driven lung cancer have limited therapeutic options after progressing on their targeted tyrosine kinase inhibitor (TKI) therapy. Given the growing role of immune checkpoint inhibitor (ICI) therapy in the treatment of lung cancer, oncogene-driven cancer has warranted further evaluation regarding ...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.1007/s40265-020-01320-0
更新日期:2020-06-01 00:00:00
abstract::Coronary arterial thrombolysis is becoming an established treatment of acute myocardial infarction. If given early enough, it recanalises occluded coronary arteries, salvages myocardial function and reduces mortality. A reduction of mortality in patients with acute myocardial infarction has now been demonstrated for s...
journal_title:Drugs
pub_type: 杂志文章,评审
doi:10.2165/00003495-198938030-00003
更新日期:1989-09-01 00:00:00
abstract::The studies reported here were designed to ascertain whether or not the new beta-lactam antibiotic, temocillin, would produce antibiotic-associated colitis in the hamster. The experiments were controlled with clindamycin and cefoxitin, which are known to induce antibiotic-associated colitis experimentally and clinical...
journal_title:Drugs
pub_type: 杂志文章
doi:10.2165/00003495-198500295-00012
更新日期:1985-01-01 00:00:00