Practice%20Based%20Research

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Practice Based Research at
Pharmacy Practice Research Specialty Practice
Unique Role and Opportunity
Research Completed in a Hospital Medical /
Clinical Pharmacy Service Related
Research Examples of Some Research to
demonstrate the breadth of the work and the
degree of opportunity possibility
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Specialty Practice Site in Pharmacy Practice
Based Research in Hospital Pharmacy
Each Profession must complete research to
advance Research improves the knowledge base
credibility and is a method of improving a
professions ability to stay current.
Pharmacy leaders are very knowledgeable in
particular areas Cardiovascular Specialty
CPR/ICU/Care Teams Ambulatory Care
Anticoagulation Programs Infectious
Diseases Rise to that level of recognition
through experience and reading/reviewing current
literature (research) related to their area of
practice.
But who does the research?
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Most Pharmacy Research is completed by
pharmacists who are Pharm D or MSc trained some
with residencies and some with post-PharmD
fellowships Many work in a specialty
environments Cardiovascular Specialty
CPR/ICU/Care Teams Ambulatory Care
Anticoagulation Programs Infectious Diseases
But how do you get there?
PHARMACY DEPARTMENT with Critical Mass with
Common Interest Ability to Complete
Research Administrative Support Time
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Sunnybrook in the 70s
Director Jim Mann Associate Director Bill
Wilson Coordinators John Iazzetta Bill
Bartle Tom Paton
Residency
Graduate Studies _at_ UofT Dr. Thiessen Kinetics
Return to Sunnybrook
Bench space grew to an 800 ft2 Quality Control
Laboratory in early 80s 2 Research Assistants /
laboratory technicians Laboratory supplies,
etc Annual operating expenditure 100K
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Current Resources
About 1500 ft2 in K-Basement Lab
Equipment
1 LC MS-MS 2 LC - UV / Fl / EC Freezers, 1
80C 1 -20C 3 computers in the lab plus 3 other
computers
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Research at Sunnybrook
Most Work has had an Analytical Requirement
IV additive Service
Pharmacokinetics
Statistics
Bioequivalence Drug-Drug-Interactions Pharmacodyna
mic Studies
Drug Stability Drug Compatibility
Tyramine Content of Food Herbal Content/Label
Claim
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All studies have been completed through
collaboration in fact for most the idea/the
need was generated by someone else a pharmacist
a physician someone with a practical question
Several types of Research Bench Research
Clinical Research Survey Research
Generally at a Hospital Funding is for a
specific single project which may take several
months or several years
Can be done anywhere Funding is often for a
specific study
Often at a University Funding is often for a
program multiple years
These are questions which relate directly to
patient care. The questions result in single
studies that answer a specific question. The
results can be used immediately in a patient
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There are numerous clinical questions for which
there is no good data. If you are a pharmacist
and you are asked such a question where do you
turn?
? In an HIV patient can we improve response to
drug therapy if we make sure that drug
concentrations are within a certain range. ? If
ciprofloxacin is given to a patient on dialysis,
will dialysis increase drug clearance, and if
so, what dose is required to replace losses. ?
If a patient has an NG tube, can I crush a
nifedipine PA tablet Will the patient experience
the same clinical response or must I convert
to IV therapy.
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Simpler questions
? If a patient is taking a herbal medication
will it interfere with other drug therapy? ? If
you have 10 different herbal preparations on the
shelf what one is best? ? If the manufacturer
of a 300 /IV dose drug says that the drug must
be discarded if it is not used immediately,
should I discard the medication? ? Can
dolasetron and dexamethasone be mixed in the
same IV container prior to administration to a
patient.
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All studies have been completed through
collaboration in fact for most the idea/the
need was generated by someone else a pharmacist
a physician someone with a practical question
Scientific Abstracts Papers John Iazzetta
21 11 Tom Paton 16
14 Bill Bartle 11 12 Sandra Tailor
5 26 Brian Hardy 2
9 Sharon Yamashita 1 5
Graduate Students Lee Dupuis Yana Bacjar Ina
Sungaila Debra Kwan Carrie Fung Fran
Paradiso-Hardy Robert Lepage
Information current to December 2001
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Examples of studies completed
A pharmacist a physician asks a question,
we try to respond

1. Compatibility Study
2. Stability Studies
3. Bioequivalence study Iron
4. Tyramine in food
5. Evaluation of content of Herbals
6. Use of handhelds in Clinical Pharmacy

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Compatibility Studies.
In hospitals, most patients will only have 1
intravenous line running at anyone time. What do
you do when a patient has multiple intravenous
drugs? Can you give them together ? or will
they ppte in the line? You could given them
sequentially and then flush the line with
saline. But this will require excessive nursing
time. You could start a second intravenous line
patient? You could test the compatibility.
Most studies look at two drugs and present the
results in a table
Hydromorphone 2 mg/mL 10
mg/mL 40mg/mL Cefazolin 20 mg/mL in D5W
C C C Cefazolin 300
mg/mL I recon vial I I
I
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Compatibility of dexamethasone sodium phosphate
with hydromorphone hydrochloride or
diphenhydramine hydrochloride SCOTT E. WALKER,
CARLO DEANGELIS, JOHN IAZZETTA, J. GARY
EPPEL Am J Hosp Pharm 48 2161-6 1991
When equal volume of dexamethasone (10 mg/mL) and
diphenhydramine (50 mg/mL) are mixed a clear but
water immiscible liquid is observed. This
incompatibility is not visually apparent at lower
concentrations. is this due to
compatibility or visual acuity?
Equal vol. hydromorphone 50 mg/mL and
dexamethasone 2 mg/mL are compatible but
hydromorphone 40 mg/mL and dexamethasone 10
mg/mL are incompatible
Are these examples of concentration dependant
compatibilities?
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Develop a method for hydromorphone
(H), Dexamethasone (Dx), methylparaben (M),
propyl paraben (P), creatinine (C) and
degradation products (Dx-1) Then measure
concentrations.
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Dexamethasone Diphenydramine
Equal volumes of D 50 Dex 10
Equal volumes of D 50 Dex 4
Region of Compatibility
Region of Incompatibility
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Compatibility Studies
Similar graphs have been published for
Hydromorphone Heparin Dexamethasone
Diphenhydramine Dexamethasone Midazolam Insulin
Labetalol Insulin Norepinephrine Insulin
dopamine Heparin Labetolol Heparin dopamine
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Stability Studies
Manufacturers provide many intravenous drugs as
lyophilized powders. monograph states that
following reconstitution that the product should
be used immediately (with 24 hours).
In most hospital settings, this can contribute
to wastage. 24 hours is too little time for a
change in dose or a discontinued (unused) IV
medication to be re-labeled and given to a
second patient.
Can the expiry date be extended?
Wastage seems to be related to the Shelf-life.
You need time to get the IV dose to a second
patient. But can you move a drug along the line?
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Stability Studies
But can you move a drug along the line? And
why would you want to?
Each dose 30. The top dug on the list in
1986 was cefazolin. With wastage at only 4
monthly expenditures gt 16,500. If we used a 24
hour expiry date, wastage could have been 2640
/ month (31,600 per year). Systematic
evaluation of stability and completed the
studies which demonstrated expiry dates could
be extended to 7 days or more. Wastage was
eventually reduced to less than 3
Savings in 1986 80,000.00 2001 148,000.00
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Bioavailability Studies
Head of Hematology presents two cases of anemia
unresponsive to Enteric Coated Ferrous Sulfate
tablets
Poor clinical response to enteric-coated iron
preparations. RUDINSKAS L, PATON TW, WALKER SE,
DOTTEN DA, COWAN DH. Can Med Assoc J.
1989. 141 565-566.
Problem was that patients responded well
quickly to oral liquid formulations of ferrous
sulfate.
Was it possible that Enteric Coated Ferrous
Sulfate Tablets were not being absorbed? but
they had been on the market since the mid 60s..!!
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Bioavailability of oral ferrous sulfate
preparations in normal volunteers. WALKER SE,
PATON TW, COWAN DH, MANUEL MA, AND DRANITSARIS G.
Can Med Assoc J. 1989. 141 543-547.
Enteric Coated FeSO4 tablets had
bioavailability of less than 25 a
negative bioavailability was estimated for 1
brand DQTC listing
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Label Accuracy of Herbal Products
Your pharmacy stocks several brands of a
particular herbal preparation. What brand should
you recommend to patients? Or if you only have
limited space what brand should you stock?
A January 2000 STAR report evaluated 10 brands
of each of ginseng, garlic and feverfew,
finding between 0 85 of label claim in each.
Its open season on the consumer. When you buy
one of these products, its an act of faith
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Estimating the Concentration of Hypericin(s) in
Commercial Products
54 different St Johns wort preparations were
purchased
14 US preparations (no tinctures) 4
Walmart (Pittsburgh) 7 Rite Aid Pharmacy
in Virginia Beach 3 From 2 other
Pharmacies in Virginia Beach
40 Products purchased from Retail Stores in GTA
Pharmacies, Health Food Stores, Grocery Stores
12 Tablets 26 Capsules 16 Tinctures
Hypericin and pseudohypericin concentrations
were determined by chromatography
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CAPSULE RESULTS
26 Formulations
Mean Potency 56.67
Naturalife
Range 0 - 108.62
Herb Tech
Canadian Potency 50.26 US Potency 60.63
p 0.2611
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TABLETS
TINCTURES
RESULTS
16 Formulations
The median concentration of a tincture was 6.49
?g/ml. In order to provide a dose similar to
the median capsule or tablet, you would have to
ingest more than 70 mL / dose. Most tinctures
come in dropper bottles of 50 mL or less.
12 Formulations
Mean Potency 53.57
Mean Concentration 23.1 ?g/mL
Range 0 - 110 ?g/mL
Range 5.46 - 81.35
5 mL of Herbal Factors delivers 550 ?g Label
Rec. 1 mL Equivalent to average Tab or cap
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LIMITATIONS

• Analysis consisted of only 1 lot
• Only naphthodianthrones measured

Next study evaluated the parthenolide content in
Feverfew products, looking at different lots.
Most Feverfew products are standardized to 0.2
but some are as high as 0.7 parthenolide
44 different lots of Feverfew products 14 brands
of capsules (23 lots), 9 brands tablet/caplet (15
lots) and 6 Tinctures (8 lots) All purchased in
Southern Ontario, 1999
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Feverfew Products Percent of Label Claim
Range of Label Claims Across all brands lt 8.4
to 446 Median 72 2/3 are less than 100
Brands 14 Caps 9 Tabs 6 Tinctures No label
claim for 5 Caps and all 6 Tinctures
18 brands, 30 different lots with label claims
Percent of label claim
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Feverfew Products Percent of Label Claim
Range of Label Claims within a brand 17 ? 42 ?
110 101 ? 169? 184
Brands 14 Caps 9 Tabs 6 Tinctures No label
claim for 5 Caps and all 6 Tinctures
18 brands, 30 different lots with label claims
Percent of label claim
Range of Label Claims Within a Brand 418
446 58, 65 66
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Alternative Product Content Result Summary
St Johns Wort. 54 brands, single lots
Content varies from 0-108 of Label Claim
Feverfew 29 brands, 44 lots
Content varies from lt 8.4 to 446 of label Claim
Valerian 19 brands, 30 lots
Content varies from 36 to 227 of label Claim
Glucosamine 53 brands, 77 lots
Content varies from 39 to 134 of label Claim
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Tyramine Content of Food
Why? In normals, 450 mg of tyramine increases BP
30 mmHg in 50 of subjects In patient on MAO
inhibitors, 8 mg increased blood pressure by 30
mmHg.
cheese effect was reported in 1963
hypertensive crisis following ingestion of
cheese. Severe headache nausea some deaths
Problem case reports of patients on MAOI with
headache following ingestion of a food
restriction of the food restricted food list
grows to include 200 items.
Question Experimentation by patients is
dangerous Can we produce a list that contains
only tryramine containing foods?
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Tyramine Content of Food
Dietary restriction, tyramine and the use of
monoamine oxidase inhibitors
Shulman KI, Walker SE, MacKenzie S and Knowles S.
J clin Psychopharmacol. 1989. 9 397-402.
Analysed 111 foods. Identified several foods
(some immature, non-aged cheeses and Chianti
Wine) that did not require restriction
Hypertensive Episode Associated with phenelzine
and Tap Beer A re-analysis of the Role of
Pressor Amines in Beer. Tailor, SAN, Shulman KI,
Walker SE, Moss J, Gardner D. J Clin
Psycopharmacol 1994 14 5-14
79 brands of beer, 98 different samples 38
different brands of tap beers, 30 different
canned bottled beer, 11 dealcoholized beers
4 tap beers containing more than 27 mg/L of
tyramine
Pizza, combination foods sausage .
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Handhelds in Pharmacy
Organization tools Email, Date/Appointments
/ Addresses phone Numbers
Medical based programs ePocrates RxTM, Clinical
Drug Database ePocrates RxTM, Infectious Disease
Guide
Patient Tracking Software Pendragon
software ePatient 2000
Could you get these devices programs to help
you work more efficiently? Identify patients at
risk, gather workload stats, Calculate the cost
savings of a clinical recommendation
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Other Current Studies
Clinical Trials Evaluation of the Effectiveness
of TDM for PI in HIV patients Weekly analysis
of PI concentrations in plasma and integration of
concentration with HIV virus phenotype
to adjust PI dosing. Evaluation of THC to
improve appetite in HIV patients
Development and analysis of THC, OH COOH
metabolite concentrations in 32 subjects
receiving multiple doses of 2, 4, 8
Stability / Compatibility / Analytical
Studies Compatibility Stability of
Pantoprazole Stability of a new formulation of
Docetaxel
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Sources of Funding Pharmaceutical Firms Peer -
Review Agencies Ontario Ministry of Heath Ontario
HIV Treatment Network Physician Services
Incorporated Canadian Institute of Health
Research Local Hospital Funding Profit from
Pharmaceutical Contract work
Collaborators at Sunnybrook John Iazzetta Tom
Paton Bill Bartle Sandra Tailor Brian
Hardy Sharon Yamashita