Davita research presentation
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Transcript of Davita research presentation
Clinical Research on fast vs. fed states affecting the PK and PD parameters of medicationsDaniel LeUNMC College of Pharmacy
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
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
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 !
Recommendations on Designing Fed-Fast Studies by FDA
• General Design• Subject Selection• Dosage Strength• Test Meal• Administration• Sample Collection• Data Analysis
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
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
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
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
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
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
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
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
Data Analysis• Total Exposure (AUC)• Peak Exposure (Cmax)• Time to peak
exposure (Tmax)• Half-Life
( elimination)• For modified-release
products also include lag-time
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
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.
Examples Articles of Research
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.
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
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
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
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
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 !
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
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
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
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
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
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
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
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
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