Transcript Food and Drug Interactions

Food and Drug Interactions
Sloan-Kettering Institute
Mark G. Klang, PhD (cand), RPh, BCNSP
Research Pharmacy Supervisor
Overview
• Drug issues
– ADME
• Administration
issues
– Drugs through
feeding tubes
– Compatibility of
injectable drugs
• Stability of
ingredients
• Vitamin stability
• Contaminants
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
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
Tablet breakup
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
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
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
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
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
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
PEG and PEJ
Issues with Route of
Administration
Physical 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
Median % Drug Lost
in Ensure compared with H2O
90
82.5
80
70
61.3
60
45.8
50
% Lost
40
30
20
10
0
Ciprofloxacin
Ofloxacin
Levofloxacin
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
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 ??
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
U.S.P. Drug Problem Product Report
Stools & Drug Doses per Hospital Day
10
8
6
4
2
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19
Hospital Day
# Stools
# Diphenoxylate
# Loperamide
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.
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
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
Interface Interactions
++
(-)
(-)
(-)
Ca
(-)
(-)
(-)
(-)
AA
oil
(-)
AA
zeta potential
interface
Sample B vs Filtered B
35000
30000
25000
Filtereed
TNA B
20000
15000
10000
5000
Particle Size nm
467
320
220
150
103
-5000
71
48
33
23
16
11
7
5
3
2
2
1
0
Filtering TNA
Lipid
Droplet
1.2 Micron (+)
Filter
Ink bottle Effect
Intravenous Compatibility
• pH - acid base
interactions
• Concentration Vancomycin and
ceftazidime.
• Crystal formation –
Ascorbic Acid
• Precipitate
formation – Ca +
PO4
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
Phenytoin
• Controlled studies do not find
interaction
• Only occurs in case reports
• In-vitro studies document the
occurrence – but fail to show
mechanism
Phenytoin
• Suspension formulation is very thick
• Adheres to surfaces – increases
dosing errors
• Diluting drug improves dissolution
Phenytoin Dissolution
25
12.5
6.25
20
15
10
5
0
-5
-10
-15
-20
Water
Osmolite CaCasein
Suspension
water
Osmolite CaCasein
Tablet
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
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
Warfarin Binding
Warfarin recovery when mixed with chopped feeding tubes
in water
1.5
1
0.5
0
5mg
5 mg /FT
10mg/FT
15 mg/FT
add 2X FT
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
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
Tigacycline
•
•
•
•
Structurally similar to tetracycline
Tetracycline is inactivated by metal
Is tigalcycline affected?
Being studied now
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
MAOI
• Sensitivity to tyramine
– causes hypertension
• Some antidepressants
(new patch),
antibiotics,
chemotherapy
• Found in NYS extrasharp cheddar cheese,
Chianti and beer
Steroids – Nutrition issues
• Patient education essential
• Increased loss of electrolytes (K)
retention of Na.
• Increased glucose level
• GI irritation
• Slowly taper off
Summary
• Everything interacts
• Food shares same ADME as do
drugs
• Question all conclusive studies
• When in doubt, do more research