Abstract：
BACKGROUND:Tuberculosis (TB) causes 25% of all deaths among individuals infected with human immunodeficiency virus (HIV). Rifampicin (RIF) is a potent inducer of drug metabolizing enzymes and drug transporters, and co-administration with dolutegravir (DTG) reduces DTG exposure; this can be overcome by doubling the DTG dose to 50 mg twice daily. This study investigated the effect of RIF on DTG exposure when dosed at 100 mg once daily, which could provide an easier option than 50 mg twice daily. METHODS:An open label, pharmacokinetic (PK) study was undertaken. Healthy HIV-negative subjects received DTG 50 mg for 7 days (PK1), DTG 100 mg for 7 days (PK2), RIF for 14 days, DTG 50 mg + RIF for 7 days (PK3) and DTG 100 mg + RIF for 7 days (PK4). Steady-state full DTG PK profiles were evaluated. RESULTS:DTG geometric mean ratios (GMRs) of PK3/PK1 of maximum concentration (Cmax), area under curve (AUC24h) and 24-h post-dose concentration (C24h) were 0.65 [90% confidence interval (CI) 0.55-0.75], 0.44 (90% CI 0.37-0.52) and 0.15 (0.13-90% CI 0.17), respectively. GMRs of PK4/PK1 Cmax, AUC24h and C24h were 1.09 (90% CI 0.97-1.21), 0.74 (90% CI 0.64-0.86) and 0.24 (90% CI 0.20-0.28), respectively. Median C24h of DTG 50 mg + RIF and DTG 100 mg + RIF were 251 (range 129-706) ng/mL and 140 (range 73-426) ng/mL, respectively. CONCLUSION:Although there were substantial reductions in DTG C24h when co-administered with RIF, concentrations of both DTG 50 mg and 100 mg once daily with RIF were still above the protein-binding-adjusted IC90 (drug concentration required to inhibit 90% of in-vitro viral replication) of 64 ng/mL. Further studies in HIV-TB co-infected individuals are warranted to confirm these results.
journal_name
Int J Antimicrob Agentsjournal_title
International journal of antimicrobial agentsauthors
Wang X,Cerrone M,Ferretti F,Castrillo N,Maartens G,McClure M,Boffito Mdoi
10.1016/j.ijantimicag.2019.04.009subject
Has Abstractpub_date
2019-08-01 00:00:00pages
202-206issue
2eissn
0924-8579issn
1872-7913pii
S0924-8579(19)30095-0journal_volume
54pub_type
杂志文章abstract：:Streptococcus pyogenes is a common pathogen which may be associated with significant morbidity and mortality. Recent information is not readily available, in Canada, regarding the susceptibility of clinical isolates to penicillin, extended spectrum and/or newer agents. We collected and tested 1003 isolates of S. pyoge...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/s0924-8579(98)00105-8
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journal_title：International journal of antimicrobial agents
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doi：10.1016/s0924-8579(03)00047-5
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journal_title：International journal of antimicrobial agents
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abstract：:In this study, the in vitro activity of tigecycline against 1140 enterococci collected from humans, food products, animals and the environment in Portugal (1996-2008) was analysed. Ten isolates (seven Enterococcus faecalis and three Enterococcus spp.) non-susceptible to tigecycline (minimum inhibitory concentrations o...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
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journal_title：International journal of antimicrobial agents
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,评审
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2006.09.025
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abstract：:The aim of this study was to evaluate the effect of sodium diclofenac on the bioavailability of amoxicillin. In this randomised, crossover study with a 1-week washout period, 20 volunteers received a 2g oral dose of amoxicillin (Amoxil) (Group 1) or a 2g oral dose of amoxicillin with 100 mg of sodium diclofenac (Volta...
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pub_type： 杂志文章,随机对照试验
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,评审
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
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pub_type： 杂志文章,评审
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,评审
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/0924-8579(92)90028-p
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pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2003.09.028
更新日期：2004-05-01 00:00:00
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
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更新日期：2020-04-01 00:00:00
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2008.10.028
更新日期：2009-05-01 00:00:00
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2005.12.010
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/s0924-8579(96)00360-3
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journal_title：International journal of antimicrobial agents
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journal_title：International journal of antimicrobial agents
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journal_title：International journal of antimicrobial agents
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journal_title：International journal of antimicrobial agents
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
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更新日期：2018-09-01 00:00:00
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pub_type： 杂志文章,评审
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/0924-8579(94)90045-0
更新日期：1994-06-01 00:00:00
abstract：:Seventy laboratories in nine European countries (Belgium, France, Germany, Italy, The Netherlands, Portugal, Spain, Switzerland and the UK) each collected 100 consecutive gram-positive bacterial pathogens during 1995. MICs were determined by a co-ordinating laboratory in each country using an agar incorporation method...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,多中心研究
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journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
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