Imperial College London
Alternate

Emeritus ProfessorMyraMcClure

Faculty of Medicine, Department of Infectious Disease

Emeritus Professor of Retrovirology
 
 
 
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Contact

 

+44 (0)20 7594 3902m.mcclure

 
 
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Location

 

456Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wang:2019:10.1016/j.ijantimicag.2019.04.009,
author = {Wang, X and Cerrone, M and Ferretti, F and Castrillo, N and Maartens, G and McClure, M and Boffito, M},
doi = {10.1016/j.ijantimicag.2019.04.009},
journal = {International Journal of Antimicrobial Agents},
pages = {202--206},
title = {Pharmacokinetics of dolutegravir 100 mg once-daily with rifampicin},
url = {http://dx.doi.org/10.1016/j.ijantimicag.2019.04.009},
volume = {54},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundTuberculosis (TB) causes 25% of all deaths among HIV-infected individuals. Rifampicin (RIF) is a potent inducer of drug metabolising enzymes and drug transporters and co-administration with dolutegravir (DTG) reduces DTG exposure, which can be overcome by doubling the DTG dose to 50 mg twice-daily. We investigated the effect of RIF on the DTG exposure when dosed at 100 mg once-daily, which could provide an easier option than 50 mg twice-daily.MethodsWe conducted an open label, pharmacokinetic (PK) study. Healthy HIV-negative subjects received DTG 50 mg for seven days (PK1), DTG 100 mg for seven days (PK2), RIF only for 14 days, DTG 50 mg plus RIF for seven days (PK3), and DTG 100 mg plus RIF for seven days (PK4). Steady state full DTG PK profiles were evaluated.ResultsDTG geometric mean ratios (GMR) (90% confidence intervals, CI) of PK3/PK1 of 50 mg Cmax, AUC24h, and C24h were 0.65 (0.55-0.75), 0.44 (0.37-0.52), 0.15 (0.13-0.17). GMR (90% CI) of PK4/PK1 Cmax, AUC24h, and C24h were 1.09 (0.97-1.21), 0.74 (0.64-0.86), 0.24 (0.20-0.28). C24h median (range) of DTG 50 mg plus RIF and DTG 100 mg plus RIF were 251(129–706) ng/mL and 140 (73-426) ng/mL, respectively.ConclusionAlthough 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 of 64 ng/mL. Further studies in HIV-TB co-infected individuals are warranted to confirm these results.Clinical trial registration number (NCT03199690)
AU  - Wang,X
AU  - Cerrone,M
AU  - Ferretti,F
AU  - Castrillo,N
AU  - Maartens,G
AU  - McClure,M
AU  - Boffito,M
DO  - 10.1016/j.ijantimicag.2019.04.009
EP  - 206
PY  - 2019///
SN  - 0924-8579
SP  - 202
TI  - Pharmacokinetics of dolutegravir 100 mg once-daily with rifampicin
T2  - International Journal of Antimicrobial Agents
UR  - http://dx.doi.org/10.1016/j.ijantimicag.2019.04.009
UR  - http://hdl.handle.net/10044/1/69133
VL  - 54
ER  -
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