Linking the Gastrointestinal Behavior of Ibuprofen with the Systemic Exposure between and within Humans—Part 2: Fed State

Autor: Duxin Sun, Bo Wen, Bart Hens, Jianghong Fan, Gregory E. Amidon, Joseph Dickens, Allen Lee, Gail Benninghoff, Marival Bermejo, Gordon L. Amidon, Jeffrey Wysocki, Paulo Paixão, Raimar Löbenberg, William L. Hasler, Arjang Talattof, Niloufar Salehi, Jason Baker, Alex Yu, Robert Lionberger, Yasuhiro Tsume, Ann Frances, Mark J. Koenigsknecht, Kerby Shedden
Rok vydání: 2018
Předmět:
Male
BIOAVAILABILITY
Administration
Oral
Datasets as Topic
Pharmaceutical Science
Ibuprofen
02 engineering and technology
Research & Experimental Medicine
buffer capacity
Pharmacology
030226 pharmacology & pharmacy
Food-Drug Interactions
CALORIC CONTENT
0302 clinical medicine
Oral administration
oral absorption
Drug Discovery
ABSORPTION
VITRO
Pharmacology & Pharmacy
IN-VIVO DISSOLUTION
ibuprofen
Biological Variation
Individual
Stomach
immediate release
Hydrogen-Ion Concentration
Middle Aged
Postprandial Period
021001 nanoscience & nanotechnology
Healthy Volunteers
Postprandial
Medicine
Research & Experimental
Area Under Curve
Molecular Medicine
Female
MEAL
0210 nano-technology
Life Sciences & Biomedicine
Tablets
medicine.drug
Adult
in vivo dissolution
Cmax
Biological Availability
Bioequivalence
Models
Biological
DOSAGE FORMS
Article
in vivo study
Young Adult
03 medical and health sciences
Pharmacokinetics
In vivo
MOTILITY
medicine
Humans
Computer Simulation
Gastric Absorption
bioequivalence
Science & Technology
business.industry
manometry
fed state
Bioavailability
Drug Liberation
Biological Variation
Population
Gastric Emptying
Solubility
LIQUIDS
local drug concentration in the GI tract
business
TRACT
Zdroj: Mol Pharm
ISSN: 1543-8392
1543-8384
5468-5478
Popis: Exploring the intraluminal behavior of an oral drug product in the human gastrointestinal (GI) tract remains challenging. Many in vivo techniques are available to investigate the impact of GI physiology on oral drug behavior in fasting state conditions. However, little is known about the intraluminal behavior of a drug in postprandial conditions. In a previous report, we described the mean solution and total concentrations of ibuprofen after oral administration of an immediate-release (IR) tablet in fed state conditions. In parallel, blood samples were taken to assess systemic concentrations. The purpose of this work was to statistically evaluate the impact of GI physiology (e.g., pH, contractile events) within and between individuals (intra and intersubject variability) for a total of 17 healthy subjects. In addition, a pharmacokinetic (PK) analysis was performed by noncompartmental analysis, and PK parameters were correlated with underlying physiological factors (pH, time to phase III contractions postdose) and study parameters (e.g., ingested amount of calories, coadministered water). Moreover, individual plasma profiles were deconvoluted to assess the fraction absorbed as a function of time, demonstrating the link between intraluminal and systemic behavior of the drug. The results demonstrated that the in vivo dissolution of ibuprofen depends on the present gastric pH and motility events at the time of administration. Both intraluminal factors were responsible for explaining 63% of plasma Cmax variability among all individuals. For the first time, an in-depth analysis was performed on a large data set derived from an aspiration/motility study, quantifying the impact of physiology on systemic behavior of an orally administered drug product in fed state conditions. The data obtained from this study will help us to develop an in vitro biorelevant dissolution approach and optimize in silico tools in order to predict the in vivo performance of orally administered drug products, especially in fed state conditions. ispartof: MOLECULAR PHARMACEUTICS vol:15 issue:12 pages:5468-5478 ispartof: location:United States status: published
Databáze: OpenAIRE
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