PMID- 28630183
OWN - NLM
STAT- MEDLINE
DCOM- 20180502
LR  - 20181202
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 61
IP  - 9
DP  - 2017 Sep
TI  - Bioavailability of Lumefantrine Is Significantly Enhanced with a Novel 
      Formulation Approach, an Outcome from a Randomized, Open-Label Pharmacokinetic 
      Study in Healthy Volunteers.
LID - 10.1128/AAC.00868-17 [doi]
LID - e00868-17
AB  - The artemether-lumefantrine combination requires food intake for the optimal 
      absorption of lumefantrine. In an attempt to enhance the bioavailability of 
      lumefantrine, new solid dispersion formulations (SDF) were developed, and the 
      pharmacokinetics of two SDF variants were assessed in a randomized, open-label, 
      sequential two-part study in healthy volunteers. In part 1, the relative 
      bioavailability of the two SDF variants was compared with that of the 
      conventional formulation after administration of a single dose of 480 mg under 
      fasted conditions in three parallel cohorts. In part 2, the pharmacokinetics of 
      lumefantrine from both SDF variants were evaluated after a single dose of 480 mg 
      under fed conditions and a single dose of 960 mg under fasted conditions. The 
      bioavailability of lumefantrine from SDF variant 1 and variant 2 increased up to 
       approximately 48-fold and  approximately 24-fold, respectively, relative to that of the conventional 
      formulation. Both variants demonstrated a positive food effect and a less than 
      proportional increase in exposure between the 480-mg and 960-mg doses. Most 
      adverse events (AEs) were mild to moderate in severity and not suspected to be 
      related to the study drug. All five drug-related AEs occurred in subjects taking 
      SDF variant 2. No clinically significant treatment-emergent changes in vital 
      signs, electrocardiograms, or laboratory blood assessments were noted. The solid 
      dispersion formulation enhances the lumefantrine bioavailability to a significant 
      extent, and SDF variant 1 is superior to SDF variant 2.
CI  - Copyright (c) 2017 Jain et al.
FAU - Jain, Jay Prakash
AU  - Jain JP
AD  - Novartis Healthcare Pvt. Ltd., Hyderabad, India jay_prakash.jain@novartis.com 
      joel.leong@novartis.com.
FAU - Leong, F Joel
AU  - Leong FJ
AD  - Novartis Institute for Tropical Diseases, Singapore jay_prakash.jain@novartis.com 
      joel.leong@novartis.com.
FAU - Chen, Lan
AU  - Chen L
AD  - Novartis Institutes for BioMedical Research, Shanghai, People's Republic of 
      China.
FAU - Kalluri, Sampath
AU  - Kalluri S
AD  - Novartis Healthcare Pvt. Ltd., Hyderabad, India.
FAU - Koradia, Vishal
AU  - Koradia V
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Stein, Daniel S
AU  - Stein DS
AD  - Novartis Pharma, East Hanover, New Jersey, USA.
FAU - Wolf, Marie-Christine
AU  - Wolf MC
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Sunkara, Gangadhar
AU  - Sunkara G
AD  - Novartis Pharma, East Hanover, New Jersey, USA.
FAU - Kota, Jagannath
AU  - Kota J
AD  - Novartis Healthcare Pvt. Ltd., Hyderabad, India.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170824
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antimalarials)
RN  - 0 (Artemether, Lumefantrine Drug Combination)
RN  - 0 (Artemisinins)
RN  - 0 (Drug Combinations)
RN  - 0 (Ethanolamines)
RN  - 0 (Fluorenes)
RN  - F38R0JR742 (Lumefantrine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antimalarials/*pharmacokinetics
MH  - Area Under Curve
MH  - Artemether, Lumefantrine Drug Combination
MH  - Artemisinins/pharmacokinetics
MH  - Biological Availability
MH  - Drug Combinations
MH  - Ethanolamines/*pharmacokinetics
MH  - Female
MH  - Fluorenes/*pharmacokinetics
MH  - Healthy Volunteers
MH  - Humans
MH  - Lumefantrine
MH  - Male
MH  - Middle Aged
MH  - Young Adult
PMC - PMC5571342
OTO - NOTNLM
OT  - antimalarial agents
OT  - bioavailability
OT  - lumefantrine
OT  - malaria
OT  - solid dispersion
EDAT- 2017/06/21 06:00
MHDA- 2018/05/03 06:00
PMCR- 2017/08/24
CRDT- 2017/06/21 06:00
PHST- 2017/04/26 00:00 [received]
PHST- 2017/06/09 00:00 [accepted]
PHST- 2017/06/21 06:00 [pubmed]
PHST- 2018/05/03 06:00 [medline]
PHST- 2017/06/21 06:00 [entrez]
PHST- 2017/08/24 00:00 [pmc-release]
AID - AAC.00868-17 [pii]
AID - 00868-17 [pii]
AID - 10.1128/AAC.00868-17 [doi]
PST - epublish
SO  - Antimicrob Agents Chemother. 2017 Aug 24;61(9):e00868-17. doi: 
      10.1128/AAC.00868-17. Print 2017 Sep.