PMID- 20489027
OWN - NLM
STAT- MEDLINE
DCOM- 20110421
LR  - 20151119
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 51
IP  - 2
DP  - 2011 Feb
TI  - The effect of lopinavir/ritonavir and darunavir/ritonavir on the HIV integrase 
      inhibitor S/GSK1349572 in healthy participants.
PG  - 237-42
LID - 10.1177/0091270010371113 [doi]
AB  - S/GSK1349572 is an unboosted, once-daily integrase inhibitor with a novel 
      resistance profile. As standard of care for patients infected with HIV is 
      combination therapy, the potential interaction between S/GSK1349572 and 
      ritonavir-boosted protease inhibitors was evaluated. In an open-label, 
      repeat-dose, 2-period, 2-sequence crossover study in healthy participants, 
      S/GSK1349572 was administered at 30 mg once daily for 5 days, followed by 
      randomization to lopinavir/ritonavir 400/100 mg twice daily or 
      darunavir/ritonavir 600/100 mg twice daily coadministered with S/GSK1349572 30 mg 
      once daily for 14 days. There was no washout between periods. Serial 
      pharmacokinetic (PK) samples and safety assessments were obtained throughout the 
      study. Thirty of 31 participants completed the study (15 participants per group). 
      Treatment comparisons of steady-state S/GSK1349572 PK parameters demonstrated 
      that coadministration of lopinavir/ritonavir had no significant effect on 
      steady-state PK of S/GSK1349572. Coadministration of darunavir/ritonavir resulted 
      in a nonclinically significant reduction in steady-state plasma S/GSK1349572 
      exposures. Plasma S/GSK1349572 AUC((0-tau)), C(max), and C(tau) decreased by 22%, 
      11%, and 38%, respectively, on average. S/GSK1349572 was well tolerated with no 
      serious adverse events (AEs) or withdrawals due to drug-related AEs. The most 
      frequent drug-related AEs were diarrhea, dizziness, and headache. No dosage 
      adjustment for S/GSK1349572 is required when used with lopinavir/ritonavir or 
      darunavir/ritonavir.
FAU - Song, Ivy
AU  - Song I
AD  - GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
FAU - Min, Sherene S
AU  - Min SS
FAU - Borland, Julie
AU  - Borland J
FAU - Lou, Yu
AU  - Lou Y
FAU - Chen, Shuguang
AU  - Chen S
FAU - Patel, Parul
AU  - Patel P
FAU - Ishibashi, Toru
AU  - Ishibashi T
FAU - Piscitelli, Stephen C
AU  - Piscitelli SC
LA  - eng
PT  - Comparative Study
PT  - Controlled Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20100520
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Drug Combinations)
RN  - 0 (HIV Integrase Inhibitors)
RN  - 0 (HIV Protease Inhibitors)
RN  - 0 (Pyrimidinones)
RN  - 0 (Sulfonamides)
RN  - 2494G1JF75 (Lopinavir)
RN  - O3J8G9O825 (Ritonavir)
RN  - YO603Y8113 (Darunavir)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - Cross-Over Studies
MH  - Darunavir
MH  - Drug Combinations
MH  - HIV Integrase Inhibitors/administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - HIV Protease Inhibitors/administration & dosage/pharmacology
MH  - Humans
MH  - Lopinavir
MH  - Male
MH  - Middle Aged
MH  - Pyrimidinones/administration & dosage/*pharmacology
MH  - Ritonavir/administration & dosage/*pharmacology
MH  - Sulfonamides/administration & dosage/*pharmacology
MH  - Young Adult
EDAT- 2010/05/22 06:00
MHDA- 2011/04/22 06:00
CRDT- 2010/05/22 06:00
PHST- 2010/05/22 06:00 [entrez]
PHST- 2010/05/22 06:00 [pubmed]
PHST- 2011/04/22 06:00 [medline]
AID - 0091270010371113 [pii]
AID - 10.1177/0091270010371113 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2011 Feb;51(2):237-42. doi: 10.1177/0091270010371113. Epub 2010 
      May 20.