PMID- 31173674
OWN - NLM
STAT- MEDLINE
DCOM- 20200804
LR  - 20200804
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 8
IP  - 7
DP  - 2019 Oct
TI  - Assessment of Drug Interaction Potential Between the Hepatitis C Virus 
      Direct-Acting Antiviral Agents Elbasvir/Grazoprevir and the Nucleotide Analog 
      Reverse-Transcriptase Inhibitor Tenofovir Disoproxil Fumarate.
PG  - 962-970
LID - 10.1002/cpdd.701 [doi]
AB  - Treatment of individuals coinfected with hepatitis C virus (HCV) and human 
      immunodeficiency virus (HIV) requires careful consideration of potential 
      drug-drug interactions. We evaluated the pharmacokinetic interaction of the 
      direct-acting antiviral agents elbasvir and grazoprevir coadministered with the 
      nucleotide reverse transcriptase inhibitor tenofovir disoproxil fumarate (TDF). 
      Three open-label, multidose studies in healthy adults were conducted. In the 
      first study (N = 10), participants received TDF 300 mg once daily, elbasvir 50 mg 
      once daily, and elbasvir coadministered with TDF. In the second study (N = 12), 
      participants received TDF 300 mg once daily, grazoprevir 200 mg once daily, and 
      grazoprevir coadministered with TDF. In the third study (N = 14), participants 
      received TDF 300 mg once daily and TDF 300 mg coadministered with coformulated 
      elbasvir/grazoprevir 50 mg/100 mg once daily. Pharmacokinetics and safety were 
      evaluated. Following coadministration, the tenofovir area under the plasma 
      concentration-time curve to 24 hours and maximum plasma concentration geometric 
      mean ratios (90% confidence intervals) for tenofovir and coadministered drug(s) 
      versus tenofovir were 1.3 (1.2, 1.5) and 1.5 (1.3, 1.6), respectively, when 
      coadministered with elbasvir; 1.2 (1.1, 1.3) and 1.1 (1.0, 1.2), respectively, 
      when coadministered with grazoprevir; and 1.3 (1.2, 1.4) and 1.1 (1.0, 1.4), 
      respectively, when coadministered with the elbasvir/grazoprevir coformulation. 
      TDF had minimal effect on elbasvir and grazoprevir pharmacokinetics. Elbasvir 
      and/or grazoprevir coadministered with TDF resulted in no clinically meaningful 
      tenofovir exposure increases and was generally well tolerated, with no deaths, 
      serious adverse events (AEs), discontinuations due to AEs, or laboratory AEs 
      reported. No dose adjustments for elbasvir/grazoprevir or TDF are needed for 
      coadministration in HCV/HIV-coinfected people.
CI  - (c) 2019, The American College of Clinical Pharmacology.
FAU - Feng, Hwa-Ping
AU  - Feng HP
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Guo, Zifang
AU  - Guo Z
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Caro, Luzelena
AU  - Caro L
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Talaty, Jennifer E
AU  - Talaty JE
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Mangin, Eric
AU  - Mangin E
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Panebianco, Deborah
AU  - Panebianco D
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Fandozzi, Christine
AU  - Fandozzi C
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Zhu, Yali
AU  - Zhu Y
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Marshall, William
AU  - Marshall W
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Huang, Xiaobi
AU  - Huang X
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Hanley, William D
AU  - Hanley WD
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Jumes, Patricia
AU  - Jumes P
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Valesky, Robert
AU  - Valesky R
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Martinho, Monika
AU  - Martinho M
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Butterton, Joan R
AU  - Butterton JR
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Iwamoto, Marian
AU  - Iwamoto M
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Yeh, Wendy W
AU  - Yeh WW
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190607
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Antiviral Agents)
RN  - 0 (Benzofurans)
RN  - 0 (Drug Combinations)
RN  - 0 (Imidazoles)
RN  - 0 (Quinoxalines)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 0 (elbasvir-grazoprevir drug combination)
RN  - 99YXE507IL (Tenofovir)
SB  - IM
MH  - Adult
MH  - Antiviral Agents/administration & dosage/adverse effects/*pharmacokinetics
MH  - Area Under Curve
MH  - Benzofurans/administration & dosage/adverse effects/*pharmacokinetics
MH  - Drug Administration Schedule
MH  - Drug Combinations
MH  - Drug Interactions
MH  - Female
MH  - HIV/drug effects
MH  - Healthy Volunteers
MH  - Hepacivirus/drug effects
MH  - Humans
MH  - Imidazoles/administration & dosage/adverse effects/*pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Quinoxalines/administration & dosage/adverse effects/*pharmacokinetics
MH  - Reverse Transcriptase Inhibitors/administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Tenofovir/administration & dosage/adverse effects/*pharmacokinetics
MH  - Young Adult
OTO - NOTNLM
OT  - HIV/AIDS
OT  - clinical pharmacology
OT  - drug-drug interactions
OT  - hepatitis C
EDAT- 2019/06/08 06:00
MHDA- 2020/08/05 06:00
CRDT- 2019/06/08 06:00
PHST- 2018/09/26 00:00 [received]
PHST- 2019/05/07 00:00 [accepted]
PHST- 2019/06/08 06:00 [pubmed]
PHST- 2020/08/05 06:00 [medline]
PHST- 2019/06/08 06:00 [entrez]
AID - 10.1002/cpdd.701 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2019 Oct;8(7):962-970. doi: 10.1002/cpdd.701. Epub 2019 
      Jun 7.