To assess the effect of short term starvation and short term high fat feeding on drug metabolism of different drugs, metabolized by different metabolic pathways in healthy subjects using a cocktail approach.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
farmacokinetiek van geneesmiddelen en galzouten, niet specifiek tbv een/meerdere aandoeningen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary study endpoint is the difference in area under the plasma concentration
versus time curve (AUC) for each drug following the administration of the drug
cocktail after 36 hours of starvation (A2,A5) and after 3 days of a high fat
meal (A3,A6) in comparison with the control situation of an overnight fast
(A1,A4).
Secondary outcome
Secondary endpoints include the difference in the PK parameters clearance,
volume of distribution, absorption rate, mean residence time and elimination
half-life.
Furthermore, to study the effect of nutritional conditioning on first pass
metabolism, the difference in area under the plasma concentration versus time
curve (AUC) of the intravenous (A4,A5,A6) and oral (A1,A2,A3) drug cocktail
will be studied.
Also, the effect of short term starvation and short term high fat diet on
metabolic parameters, such as postprandial glucose, insulin, GLP-1, FGF 19 and
bile acid levels will be assessed.
Background summary
The activity of many enzyme systems in the liver is modulated by nutritional
factors. Although hardly studied in humans, there are indications that
nutritional conditioning, i.e. the composition of the previous nutrition,
influences drug metabolism and bile acid metabolism. Therefore, nutritional
conditioning may contribute to both inter- and intra-individual variations in
drug metabolism.
Study objective
To assess the effect of short term starvation and short term high fat feeding
on drug metabolism of different drugs, metabolized by different metabolic
pathways in healthy subjects using a cocktail approach.
Study design
Open-label, single-dose crossover intervention study
Intervention
This study consists of six treatment arms (N=9 per arm). Subjects will be
randomized for the sequence in which they receive a single oral (A1,A2,A3) or
intravenous (A4,A5,A6) administration of a drug cocktail and a standardized
meal (Nutridrink) (A1, A4) after an overnight fast (controls) , (A2, A5) after
36h of starvation, (A3, A6) after 3 days of a high fat meal. The oral drug
cocktail consists of: 100mg caffeine, 5mg warfarin, 20mg omeprazole, 100mg
metoprolol and 0.03mgkg-1midazolam. The intravenous drug cocktail consists of:
50mg caffeine, 5mg warfarin, 20mg omeprazole, 20mg metoprolol and 0.015mgkg-1
midazolam.
Study burden and risks
The burden of this study includes a screening visit, six 1-day 12-hour hospital
admissions, two overnight fasts, two periods of 36h of starvation, two times
three days of a high fat meal, six administrations of the drug cocktail (3x
oral and 3x intravenous), six standardized meals (Nutridrink). Bloodsamples
(n=13 samples of 4,5ml, n=12 samples of 2,0ml and 6x an intravenous catheter)
will be drawn for PK analysis and monitoring of laboratory parameters. A total
volume of about 499ml blood will be obtained in a period of eight months. For
the healthy volunteers the risks are low. This study will generate information
regarding the drug metabolizing activity during nutritional conditioning and
may therefore be of future benefit for patients with differences in nutritional
status using medication.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- Healthy (determined by an experienced physician) male of 18 years or older at the time of signing the informed consent.
- Normal renal and liver function
- Capable of giving written informed consent and to comply with the requirements and restrictions listed in the informed consent form
Exclusion criteria
- Major illness in the past 3 months
- Gastrointestinal disease which may influence drug absorption,
- Abnormalities in ASAT / ALAT / Bilirubin / gammaGT / AF laboratory data
- Drug abuse or alcoholism (>3 units of alcohol per day)
- Participation in another clinical trial in the past 12 months,
- Difficulty in donating blood or limited accessibility of a vein
- Use of tobacco products (induction liver enzymes)
- (chronisch) gebruik van medicatie
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL40834.018.12 |