This document discusses the importance of clinical research on the effects of the fed vs. fast state on medication pharmacokinetics and pharmacodynamics. It provides examples of past research that have looked at how food intake can impact drug absorption, efficacy, and safety. The document also reviews FDA guidance on designing fed vs. fast clinical studies, including recommendations on subject selection, dosage, test meals, administration, sample collection, and data analysis. Examples of specific drugs that have been studied, such as omeprazole, pantoprazole, clopidogrel, cefalexin, and abacavir are also summarized.

1. Clinical Research on
fast vs. fed states
affecting the PK and PD
parameters of
medications
Daniel Le
UNMC College of Pharmacy

2. Objectives
• Why is research important for fed vs. fast ?
• FDA’s guidance on designing fed vs. fast clinical research
• Sprinkling medication on food and liquid formulation
differences
• Results of past research that have looked at fed vs. fast drug
efficacy
• What members of allied health can do for their patients

3. Why Do Research?
• Everyone Eats
• Most people take
medications
• Medications need to be
within target range to
have efficacy and to
avoid/reduce possible
side effects
• Therefore food effecting
medication is an
important situation to
look over
• Team work for allied
health professionals

4. So Many Medications!!!!
• With so many medications
on the market and also
many that are currently in
clinical research
• Its important we are aware
of the situation, and
although its not possible to
memorize every single
medication, we must know
how to look up the
information
• Aware that there have
been pass research that
has look at the topic !

5. Recommendations on Designing
Fed-Fast Studies by FDA
• General Design
• Subject Selection
• Dosage Strength
• Test Meal
• Administration
• Sample Collection
• Data Analysis

6. Design
• Randomized
• Balanced
• Single dose
• Two Treatments (fed
vs. fast)
• Two periods of drug
administration
• Make sure that all
food is wash out
before 2nd period

7. Subject Selection
• Volunteers should be
healthy and drawn from
the general population
• Co-Morbidities often
would interfere with
results
• Larger numbers of
participants is
recommended to have
good statics credibility
• Minimum of 12 subjects
is recommended to
compete the food-effect
studies

8. Dosage
• Highest strength of a drug
in the market is preferred
to test the food effect
• Unless clinical safety is a
concern and then lower
dose should be used
• If previous studies have
been done on the highest
dose, it can also be
possible to test a smaller
dose to see how food
effects the smaller dose

9. Test Meal
• High in Fat (50% of total calories
of the meal)
• High in Calories ( 800-1000
calories)
• Balance in protein(150), fat (500-
600), and carbohydrates(250)
• The breakdown of the calories
between protein, fat, carb and
total calories should always be in
the study report
• Reason: have the greater effect
on GI physiology
• If for whatever reason the meal
test has a different caloric
breakdown then what is
mentioned above, scientific
rational for why that is

10. Test Meal (2)
• Reason: have the greater
effect on GI physiology
• Smaller meals will not
show much difference
between the fast-fed
states and therefore not
accurate to compare
• If for whatever reason
the meal test has a
different caloric
breakdown then what is
mentioned above,
scientific rational for why
that is

11. Administration
Fasted Treatment
• Overnight fast for 10
hours
• 240 ml of fluids
• No food for 4 hours after
the dose
• Water is allowed except
one hour before and one
hour after
Fed Treatment
• Overnight fast for 10 hours
then start recommended
30 minutes before drug
admin
• Eat the meal in 30 minutes
• 240 ml of water
• No food for four hours
after the dose
• Water is allowed except
one hour before and one
hour after

12. Sample Collection
• Plasma is ideal
• Make sure the time
and intervals that
blood is drawn is the
in both fed and fast
are documented
• Analysis blood for
any other disease
that are unknown
that might have an
effect on drug

13. Sample Collection (2)
• Food can have an
effect on the time
course of plasma drug
concentrations
• Therefore it is
acceptable that fasted
and fed treatments
can have different
sample collection
times

14. Data Analysis
• Total Exposure (AUC)
• Peak Exposure (Cmax)
• Time to peak
exposure (Tmax)
• Half-Life (
elimination)
• For modified-release
products also include
lag-time

15. Sprinkles
• Controlled release Capsules
• Can be sprinkled on soft
foods
• Additional studies should
be done with intact
capsules on both fed and
fast patients
• Documented that there
was no differences in
efficacy between sprinkling
the the beads onto foods
vs. swallowing a intact
capsule

16. Liquid Formulations
• Liquid medications when
mixed with a beverage
before administration
can change the BA
• Always test the solution
that is intended to mix
the medication with
• Document the liquid that
was mixed and provide
evidence that it did not
have an effect on the
medication.

17. Examples Articles of Research

18. Where ?
• Many articles from
both humans and
animals
• All the articles
mentioned will be
based on human
studies
• Have been studied
for many years
• Many different parts
of the world.

19. Alacepril
• Research done in Fukuoka, Japan
• 1985
• ACE- inhibitor use to treat hypertension
• Shows that this has been an important topic and is concern to
people for many years
• Alacepril converts to Captopril

20. Alacepril
• Fed state delayed the
tmax of free captopril,
but not significantly
• AUC was unchanged
• Fed states increases
free captopril in blood,
perhaps its because its
converted from
Alacepril after
absorption
• Fed-Fast did not sign.
role

21. Omeprazole
• According to
prescribing
information drug is to
be taken 30 minutes
prior to a meal
• Two formulas tested
Ompranyt & Mopral
• Both formulas when
taken on a high fat
diet reduces Cmax
and AUC
• Shows that drug
should be taken as
directed on a empty
stomach

22. Pantoprazole
• Two-Single dose, open
label, 7 days apart
(washout period)
randomized between 2
groups of fed or fast
• Fed State increases the
Tmax
• Fed State has more
variability (erratic
absorption)
• Fed state also takes longer
to be detected in the blood
• Similar to Omeprazole
should take as directed, 30
minutes before meal

23. Clopidogrel
• Drug vs placebo and
then the drug between
fast-fed states
• Fed vs. fast shows no
difference in
antiplatlet response (
Pharmacodynamics)
• Half-life, Tmax, Cmax,
AUC all did not have
significant difference
(Pharmacokinetic)
• Can be taken with or
without food !

24. Cefalexin
• Beta-lactam antibiotic
• 2012 in Xijing, China
• Study was done on healthy
males to determine the effect
that food has on the drug
• Two groups one group had a 8
h fast period, while the other
was postprandial
• Drugs given to both groups at
8am and 8pm daily
• Half-life and Cmax both
increased at 8pm compared
to 8am in the fed patients,
while it stayed the same in
the fasting patients

25. Cefalexin Results
• Often we
recommend
antibiotics to be
taken with food !
• Often antibiotics will
cause GI upset
• Tough situation !
• Balance between
side effects or the
efficacy of the
antibiotic

26. Abacavir
• Medication used to
treat HIV
• Was tested to see if
the generic would be
just as equally
effective as other
products
• Research also looked
at fed-fast and see if
it had a role

27. Abacavir
• Results shows that the
generic is equally effective
• Fed-Fast did not have an
effect on the efficacy of the
drug
• Examples shows that
generic vs. name brand
products, food effect is also
a concern !
• Therefore should always be
tested before it can be
considered AB equivalent

28. Conclusion
• Varies according to the
type of medication, some
types of medication will be
more effected than others
• Co-Morbidities will play a
role in the effect of the
food and how it can effect
drug efficacy
• Most of the studies have
the fed group eat food high
in calories and in fat
• Which shows that the type
of food we eat matters

29. Importance
• We can inform patients
on what medications can
they take on empty
stomach
• If medications do get
effected on full stomach
patients can determine
when would be the best
time to take medications
• Keep patients healthy
since we are keeping
their medications within
the therapeutic window

30. Importance (2)
• From the different results that
the articles provided we can
see there was variation
• Its important as members of
the allied health to understand
to the extent which
medications have are effected
by food
• In clinical research it would
determine how the studies are
designed based on the drug
being tested
• We in any setting it will be
important to know what
resources we can use to have a
more clear understanding of
food and its effect on
medications

31. What to take away?
• Why research is
important?
• Be aware of variation
that results has shown
• To understand that
there are resources
available
• At times we must use
our clinical skills to
make appropriate
recommendations

32. References
• Hurbin F., Boulenc X., Daskalakis N., Farenc C., Taylor T., Bonneau D., LaCreta, F., Cheng, S. & Sultan E.
(2012). Clopidogrel pharmacodynamics and pharmacokinetics in the fed and fasted state: A
randomized crossover study of healthy men. Journal of Clinical Pharmacology, 52(10), 1506-1515.
• Vaz-da-Silva M., Loureiro A.I., Nunes T., Maia J., Tavares S., Falcao A., Silveira, P., Almeida, L. & Soares-da-Silva P.
(2005). Bioavailability and bioequivalence of two enteric-coated formulations of omeprazole in fasting
and fed conditions. Clinical Drug Investigation, 25(6), 391-399.
• Ding Y., Jia Y.Y., Liu W.X., Lu C.T., Zhu Y.R., Yang J., Ding L.K., Yang L. & Wen A.D. (2012). Chronokinetic study of
cefalexin in postprandial and fasting volunteers. Biological Rhythm Research, 43(5), 505-513.
• Onoyama K., Hirakata H.,Tsuruda H. Ohchi, N. Tomooka, S., Motomura, K., Omae, T., Hayashi, K. & Fujishima, M.
(1985). Pharmacokinetics of a new angiotensin I converting enzyme inhibitor (alacepril) after oral
dosing in fasting or fed states. Clinical Pharmacology and Therapeutics, 38(4), 462-468.
• Rossi de Campos D., Viera N.R, Bernasconi G., Proenca Barros F.A., Meurer E.C., Marchioretto M.A., Coelho E.C.,
Calafatti S.A., Sommer C., Moreira Couto J., Buranello S. Cristino Silva A.R., Amarante A.R., Abib E., &
Pedrazzoli J. (2007). Bioequivalence of Two Enteric Coated Formulations of Pantoprazole in Healthy
Volunteers under Fasting and Fed Conditions. Arzneimittel-Forschung(Drug Research). 57(6) 309-14
• Marier J.F., Borges M., Plante G., DiMarco M., Morelli G., Tippabhotla S.K., Vijan, T., Singla, A. K. Garg M. & Monif
T. (2006). Bioequivalence of abacavir generic and innovator formulations under fasting and fed
conditions. International Journal of Clinical Pharmacology and Therapeutics, 44(6), 284-291.
• FDA Guidance for Industry, Food-Effect Bioavailability and Fed Bioequivalence Studies