PMID- 23979733
OWN - NLM
STAT- MEDLINE
DCOM- 20140514
LR  - 20211021
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 57
IP  - 11
DP  - 2013 Nov
TI  - Lack of pharmacokinetic interaction between rilpivirine and integrase inhibitors 
      dolutegravir and GSK1265744.
PG  - 5472-7
LID - 10.1128/AAC.01235-13 [doi]
AB  - Dolutegravir (DTG) and GSK1265744 are HIV integrase inhibitors (INIs) in clinical 
      development. The oral formulation of rilpivirine (RPV), a nonnucleoside reverse 
      transcriptase inhibitor (NNRTI), has been approved for treatment-naive HIV 
      infection. Long-acting depot injections of GSK1265744 and RPV are also being 
      developed. This study evaluated the potential for drug interactions between RPV 
      and these INIs. This phase 1, open-label, two-cohort, three-period, 
      single-sequence crossover study evaluated oral coadministration of RPV with DTG 
      or GSK1265744. Healthy subjects received DTG (50 mg every 24 h for 5 days) or 
      GSK1265744 (30 mg every 24 h for 12 days) in period 1 followed by a washout, RPV 
      (25 mg every 24 h for 11 or 12 days) in period 2, immediately followed by RPV (25 
      mg every 24 h) plus DTG (50 mg every 24 h) for 5 days or GSK1265744 (30 mg every 
      24 h) for 12 days in period 3. Steady-state pharmacokinetic (PK) parameters were 
      estimated using noncompartmental analysis of data collected on the last day of 
      each period. The combinations of RPV and DTG (n = 16) and of RPV and GSK1265744 
      (n = 11) were well tolerated; no grade 3 or 4 adverse events (AEs) or AE-related 
      discontinuations were observed. The 90% confidence intervals for the area under 
      the curve from time zero until the end of the dosage interval [AUC0-tau] and 
      maximum concentration of drug in serum (Cmax) geometric mean ratios were within 
      0.8 to 1.25. Following administration of DTG + RPV, DTG and RPV Ctau increased by 
      22% and 21%, respectively. Following administration of GSK1265744 + RPV, RPV Ctau 
      decreased 8%. DTG and GSK1265744 can be administered with RPV without dosage 
      adjustment for either agent. These results support coadministration of RPV with 
      DTG or GSK1265744 as either oral or long-acting depot injection regimens. (This 
      study has been registered at ClinicalTrials.gov under registration no. 
      NCT01467531.).
FAU - Ford, Susan L
AU  - Ford SL
AD  - GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
FAU - Gould, Elizabeth
AU  - Gould E
FAU - Chen, Shuguang
AU  - Chen S
FAU - Margolis, David
AU  - Margolis D
FAU - Spreen, William
AU  - Spreen W
FAU - Crauwels, Herta
AU  - Crauwels H
FAU - Piscitelli, Stephen
AU  - Piscitelli S
LA  - eng
SI  - ClinicalTrials.gov/NCT01467531
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130826
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Drug Combinations)
RN  - 0 (HIV Integrase Inhibitors)
RN  - 0 (Heterocyclic Compounds, 3-Ring)
RN  - 0 (Nitriles)
RN  - 0 (Oxazines)
RN  - 0 (Piperazines)
RN  - 0 (Pyridones)
RN  - 0 (Pyrimidines)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - DKO1W9H7M1 (dolutegravir)
RN  - FI96A8X663 (Rilpivirine)
RN  - HMH0132Z1Q (cabotegravir)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Area Under Curve
MH  - Cross-Over Studies
MH  - Drug Administration Schedule
MH  - Drug Combinations
MH  - Drug Interactions
MH  - Female
MH  - HIV Integrase Inhibitors/blood/*pharmacokinetics
MH  - Healthy Volunteers
MH  - Heterocyclic Compounds, 3-Ring/blood/*pharmacokinetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nitriles/blood/*pharmacokinetics
MH  - Oxazines
MH  - Piperazines
MH  - Pyridones/blood/*pharmacokinetics
MH  - Pyrimidines/blood/*pharmacokinetics
MH  - Reverse Transcriptase Inhibitors/blood/*pharmacokinetics
MH  - Rilpivirine
PMC - PMC3811315
EDAT- 2013/08/28 06:00
MHDA- 2014/05/16 06:00
PMCR- 2013/11/01
CRDT- 2013/08/28 06:00
PHST- 2013/08/28 06:00 [entrez]
PHST- 2013/08/28 06:00 [pubmed]
PHST- 2014/05/16 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - AAC.01235-13 [pii]
AID - 01235-13 [pii]
AID - 10.1128/AAC.01235-13 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2013 Nov;57(11):5472-7. doi: 10.1128/AAC.01235-13. 
      Epub 2013 Aug 26.