PMID- 25352040
OWN - NLM
STAT- MEDLINE
DCOM- 20160314
LR  - 20211203
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 55
IP  - 4
DP  - 2015 Apr
TI  - Effect of faldaprevir on raltegravir pharmacokinetics in healthy volunteers.
PG  - 384-91
LID - 10.1002/jcph.418 [doi]
AB  - Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor and an 
      inhibitor of UDP-glucuronosyltransferase-1A1 (UGT1A1), which is involved in 
      raltegravir clearance. Raltegravir, an HIV integrase inhibitor, may be used in 
      combination with HCV treatment in HCV/HIV co-infected patients. In this 
      open-label, 2-period, fixed-sequence study, 24 healthy volunteers (12 males) 
      received faldaprevir 240 mg and raltegravir 400 mg in 2 treatment schedules (A 
      and B) separated by a washout phase of >/=7 days: (A) twice-daily raltegravir (Days 
      1-3), once-daily raltegravir (Day 4); (B) twice-daily raltegravir and twice-daily 
      faldaprevir (loading dose, Day 1), twice-daily raltegravir and once-daily 
      faldaprevir (Days 2-5), once-daily raltegravir and once-daily faldaprevir (Day 
      6). Pharmacokinetics and safety were assessed over 132 hours post-dosing. 
      Compared with raltegravir alone, co-administration with faldaprevir led to 
      2.7-fold and 2.5-fold increases in raltegravir geometric mean AUC(tau,ss) and 
      C(max,ss), respectively, and a similar increase in raltegravir glucuronide 
      metabolite exposure. No serious adverse events (AEs) were reported and no subject 
      discontinued due to AEs. Faldaprevir and raltegravir co-administration was well 
      tolerated and resulted in a moderate increase in raltegravir exposure.
CI  - (c) 2014, The American College of Clinical Pharmacology.
FAU - Joseph, David
AU  - Joseph D
AD  - Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
FAU - Rose, Peter
AU  - Rose P
FAU - Strelkowa, Natalja
AU  - Strelkowa N
FAU - Schultz, Armin
AU  - Schultz A
FAU - Garcia, Jeanette
AU  - Garcia J
FAU - Elgadi, Mabrouk
AU  - Elgadi M
FAU - Huang, Fenglei
AU  - Huang F
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141208
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Aminoisobutyric Acids)
RN  - 0 (HIV Integrase Inhibitors)
RN  - 0 (Oligopeptides)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Quinolines)
RN  - 0 (Thiazoles)
RN  - 43Y000U234 (Raltegravir Potassium)
RN  - 958X4J301A (faldaprevir)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 2.4.1.- (UGT1A1 enzyme)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Adult
MH  - Aminoisobutyric Acids
MH  - Drug Administration Schedule
MH  - Drug Interactions/genetics
MH  - Female
MH  - Genotype
MH  - Glucuronosyltransferase/genetics
MH  - HIV Integrase Inhibitors/administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Healthy Volunteers
MH  - Humans
MH  - Leucine/analogs & derivatives
MH  - Male
MH  - Oligopeptides/administration & dosage/adverse effects/*pharmacology
MH  - Proline/analogs & derivatives
MH  - Protease Inhibitors/administration & dosage/adverse effects/*pharmacology
MH  - Quinolines
MH  - Raltegravir Potassium/administration & dosage/adverse effects/*pharmacokinetics
MH  - Thiazoles/administration & dosage/adverse effects/*pharmacology
MH  - Young Adult
OTO - NOTNLM
OT  - HIV/AIDS
OT  - clinical trials
OT  - drug interactions
OT  - infectious diseases
OT  - pharmacokinetics and drug metabolism
OT  - virology
EDAT- 2014/10/30 06:00
MHDA- 2016/03/15 06:00
CRDT- 2014/10/30 06:00
PHST- 2014/08/05 00:00 [received]
PHST- 2014/10/20 00:00 [accepted]
PHST- 2014/10/30 06:00 [entrez]
PHST- 2014/10/30 06:00 [pubmed]
PHST- 2016/03/15 06:00 [medline]
AID - 10.1002/jcph.418 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2015 Apr;55(4):384-91. doi: 10.1002/jcph.418. Epub 2014 Dec 8.