Food and Drug Interactions Sloan-Kettering Institute Mark G. Klang, PhD (cand), RPh, BCNSP Research...
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Transcript of Food and Drug Interactions Sloan-Kettering Institute Mark G. Klang, PhD (cand), RPh, BCNSP Research...
![Page 1: Food and Drug Interactions Sloan-Kettering Institute Mark G. Klang, PhD (cand), RPh, BCNSP Research Pharmacy Supervisor.](https://reader036.fdocuments.in/reader036/viewer/2022062322/56649e595503460f94b53905/html5/thumbnails/1.jpg)
Food and Drug Interactions
Sloan-Kettering Institute
Mark G. Klang, PhD (cand), RPh, BCNSP
Research Pharmacy Supervisor
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Overview
• Drug issues– ADME
• Administration issues– Drugs through
feeding tubes– Compatibility of
injectable drugs
• Stability of ingredients
• Vitamin stability• Contaminants
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Drug Issues
• ADME – Absorption
• Involves how the drug dissolves and is released in GI
– Distribution – Involves drug moving in blood stream
– Metabolism – clearance of the drug by enzymes
– Excretion – liver or kidney removal
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Absorbtion• Swallowing• Disintegration
– tablet swells– breaks up
• Dissolution– reactions with acid – faster when ionized
• Absorption– most post pyloric– in basic environment– require non-ionized state
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Tablet breakup
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Kinetic changes Liquid vs Tablet Kinetic changes Liquid vs Tablet
• Liquids absorbed faster• Onset faster• Extent of absorption
may be greater• In stomach liquids
expose drug to greater acidic degradation
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Food Interactions with Absorption
• Milk products alter pH
• Metals chelate some medications
• Some foods compete for same absorption sites
• Food speeds GI speed – reduced absorption
• Degree of significance is important
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Metabolism – Interaction with food
• Cytochrome P-450 in GI, liver Grapefruit juice made from frozen concentrate will alter this enzyme
• Many drugs for AIDS, HTN
• Effects occur 24 hours after ingestion
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Excretion
• Urine acidity will change drug excretion
• Cranberry juice will alter pH and cause higher dissolution. This occurs with sulfonamides
• Lime juice is most acidic
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Drug Administration through Feeding tubes• Most drug
products are not designed, tested, labeled nor approved for administration via feeding tube (FT)
• 13 listing in PDR
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Clogging tubes
• Lumen size / circumference (French size)
• Length – longer loops
• No residual volume in jejunum. Tubing must be flushed. Clogging is usually due to undissolved drugs
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PEG and PEJPEG and PEJ
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Issues with Route of AdministrationIssues with Route of Administration
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Physical Issues Drug Stability with Enteral FormulaPhysical Issues Drug Stability with Enteral Formula
• Admixture may result in reduced drug stability
• Examples:– Ciprofloxacin, Ofloxacin and Levofloxacin
was tested with electrolytes and Ensure
–Significant loss of drugs in Ensure
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Median % Drug Lost in Ensure compared with H2O Median % Drug Lost in Ensure compared with H2O
82.5
45.8
61.3
0
10
20
30
40
50
60
70
80
90
Ciprofloxacin Ofloxacin Levofloxacin
% Lost
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Cipro Study
• Prepared 3 concentrations in SGF
• 5, 2.5 and 1.25 mg/ml
• Higher dilution yielded highest dissolution and yield of the drug
• 5 mg/ml had decreased release compared to control
• Shouqian Shi and Oscar Camilo
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Osmotic Issues
• Common Side Effects associated with Enteral Nutrition – 40% of TF diarrhea caused by excipients
Diarrhea, nausea, vomiting, cramping, distention & bloating
• Is it caused by:– The Enteral Nutrition ??– The Drug Therapy ??– Both ??
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ticky - it’s a sugar
smolarity - causes diarrhea
eproducible - NOT, content changes often
loated feeling - causes gas
gnites - Cauterized diabetic bowels
heophylline - has most sorbitol
bscure - amount not on label
iquids- present in most liquid medications
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U.S.P. Drug Problem Product ReportStools & Drug Doses per Hospital Day
0
2
4
6
8
10
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Hospital Day
# Stools # Diphenoxylate # Loperamide
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Intravenous Nutrition Compatibility• Contain many ingredients
– Amino acids, dextrose, lipids, electrolytes, vitamins and trace elements
• Issues of compatibility can be significant. Precipitates can occur.
• Many patients receive medications simultaneously.
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Lipid Compatibility
• Many institutions mix lipid in same container with other ingredients
• Lipid is an oil–in–water emulsion
• Electrolytes destabilize the emulsion
• Fat droplets aggregate• Clog blood vessels –
form emboli
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Lipid Emulsion Research
• Lipids form larger droplets – but the average size remains the same.
• Repellent forces between droplets are neutralized – but zeta potential does not change
• Found accumulation in lungs of rats
• Filtering particles made droplets larger
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Interface Interactions
(-)
(-)
(-)Ca
++
(-)
(-)(-)
(-)(-)
zeta potential
AA
AA
oil
interface
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Sample B vs Filtered B
-5000
0
5000
10000
15000
20000
25000
30000
35000
1 2 2 3 5 7
11 16
23
33
48
71
10
3
15
0
22
0
32
0
46
7
Particle Size nm
Filtereed
TNA B
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Filtering TNA
1.2 Micron (+) Filter
LipidDroplet
Ink bottle Effect
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Intravenous Compatibility
• pH - acid base interactions
• Concentration - Vancomycin and ceftazidime.
• Crystal formation – Ascorbic Acid
• Precipitate formation – Ca + PO4
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Phenytoin compatibility with enteral nutrition• Neurology patients
get this drug through feeding tube.
• When given with nutrition – levels drop
• Recommendations to hold feeding 2 hours before and after and increase dose
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Phenytoin
• Controlled studies do not find interaction
• Only occurs in case reports
• In-vitro studies document the occurrence – but fail to show mechanism
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Phenytoin
• Suspension formulation is very thick
• Adheres to surfaces – increases dosing errors
• Diluting drug improves dissolution
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Phenytoin Dissolution
-20
-15
-10
-5
0
5
10
15
20
Water Osmolite CaCasein water Osmolite CaCasein
Suspension Tablet
25
12.5
6.25
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Warfarin
• Anticoagulant used to reduce strokes• Inactivated by Vitamin K - broccoli• Enteral nutrition products contain Vitamin
K.• Warfarin activity drops when nutrition
given• Study shows warfarin binds to protein at
pH 8
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Warfarin Binding
• pH 8 is not physiological
• This drug binds to plastic
• It adheres to feeding tube
• It binds to protein once absorbed, but not in the stomach at pH 1.2
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Warfarin Binding
Warfarin recovery when mixed with chopped feeding tubes in water
0
0.5
1
1.5
5mg 5 mg /FT 10mg/FT 15 mg/FT add 2X FT
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Emend (aprepant)
• Anti-nausea drug• Available in capsule
which can be opened.• Can this be given
through feeding tube?• The drug is insoluble in
water• Studying
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Vitamin C – Ascorbic Acid
• High doses advised for flu and ills• Limited absorption dependent on
concentration.– More ingested = lower percent absorbed
• Higher levels produce faster excretion• High excretion will continue after high
doses stopped
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Tigacycline
• Structurally similar to tetracycline
• Tetracycline is inactivated by metal
• Is tigalcycline affected?
• Being studied now
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Aluminum
• Found in many drugs as a contaminant
• Evaluating impact on stability
• FDA attempting to legislate changes in amount
• Causes bone loss, Alzheimer's?– Linked to calcium
injection
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MAOI
• Sensitivity to tyramine – causes hypertension
• Some antidepressants (new patch), antibiotics, chemotherapy
• Found in NYS extra-sharp cheddar cheese, Chianti and beer
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Steroids – Nutrition issues
• Patient education essential
• Increased loss of electrolytes (K) retention of Na.
• Increased glucose level
• GI irritation
• Slowly taper off
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Summary
• Everything interacts
• Food shares same ADME as do drugs
• Question all conclusive studies
• When in doubt, do more research
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