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hello all
I am currently writing an introduction to pharmacokinetics and i
would like some thoughts about 2 questions i have. The first one is
about novel media for conducting pharmacokinetic studies. Usually PK
studies are done using serum or plasma or blood from (what i can
tell) therefore i was wondering if anyone knows of any other media
which could be used. So far i have found an article suggesting an
equivalence between saliva methylpredisonlone and blood levels and
one which i think suggests that caffeine in patients breath may be
related to blood levels. Obviously these are more convenient methods
of sampling patients than taking blood. So can anyone think of any
other examples of samples which have been shown to be equivalent to
boood, serum or plasma levels which could potentially be used for a
PK study?
My second question is that it seems to me that serum levels are
favoured for monitoring of drug levels. Why do we use serum instead
of plasma or blood ? or have i got the wrong end of the stick ? In
fact does it actually matter whether a PK study uses blood levels
instead of plasma or serum levels.
Your help and thoughts would be very much appreciated
Paul
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The following message was posted to: PharmPK
Dear Paul
There are other methods as well for measuring bioavailability. I have
tried to tabulate the methods along with the featuers and limitation
of each. For calrity, please copy the belw text and conver to table.
Hoping it will be of some help.
Method Basis Nature Features Limitations
Blood Data Direct; Qualitative Highly accurate Patient may be fearful
for repeated blood sampling; Fear may affect drug pharmacokinetics;
Requires extraction of drug from blood for assay of the drug in blood
Urinary Data Indirect; Quantitative Less accurate Limited to the
drugs which are excreted in significant quantities as unchanged drug
in the urine; Timely collection of the urine samples to collect total
amount of urinary drug excretion; Time consuming, i.e, requiring time
for collection of urine samples minimally up to 5 \0xD7 t\0xBD; It is
laborious method
Acute Pharmacologic Response Indirect; Qualitative Less accurate
Limited for those drugs, the pharmacological action of which can be
measured in quantitative terms
Radiometeric Indirect; Quantitative Accurate Hazards of Radioactivity
Clinical End point Indirect; Qualitative Least accurate; time
consuming Limited to the drugs the absorption of which cannot be
estimated by other methods mentioned
In-vitro dissolution Indirect; Qualitative Least accurate Limited for
the drugs which are well absorbed systemically; the absorption is
well correlated with in-vitro dissolution; drugs without known
bioavailability problems; The drugs having large margin of safety
Thanks
Nadeem Irfan Bukhari
Lecturer Pharmaceutical Technology,
International Medical University,
Bukit Jalil 57000, Kuala Lumpur, Malaysia
Web: http://www.imu.edum.my
Tel: +60 3 8656 7228, Ext. 1186; Fax: 86567229
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The following message was posted to: PharmPK
Dear Paul,
I published a paper (details below) in 2003 that used
saliva to measure paracetamol levels. Within that you will find cited a
number of other studies that used saliva for different drugs. It is not
necessarily ideal for all drugs though - if you want an indication of
blood or plasma concentration the drug needs to be able to distribute
quickly into the saliva with a Saliva:Plasma ratio close to 1. Note that
even then saliva is in equilibrium with arterial not venous blood (which
is normally used for PK studies).
Saliva is certainly less invasive for patients but is probably more
difficult to handle post-sampling. Plus you have the problem with liquid
oral dosage forms of oral contamination during ingestion which would
elevate saliva concentrations. So it can be used, but like anything has
limitations.
Another option you might want to consider is micro-dialysis probes.
Again the distribution PK will affect the relationship between plasma
and tissue levels, but perhaps at the end of the day tissue levels are
more informative anyway?
Blood vs plasma? My (probably over-simplistic) view is that plasma is
much easier to analyse so you go with what is the easiest.
Paper mentioned above:
Kennedy JM, Tyers NM, Davey AK. The influence of morphine on the
absorption of paracetamol from various formulations in subjects in the
supine position, as assessed by TDx measurement of salivary paracetamol
concentrations. Journal of Pharmacy and Pharmacology. 2003; 55(10):
1345-1350.
Andrew
Dr Andrew Davey
Senior Lecturer
Sansom Institute
School of Pharmacy and Medical Sciences
University of South Australia.
GPO Box 2471
Adelaide SA 5001
Tel: (0) 8 8302 1127
Fax: (0) 8 8302 1087
email: andrew.davey.-a-.unisa.edu.au
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The following message was posted to: PharmPK
Dear Paul,
You can mention peripheral blood mononuclear cells. This medium
sometime bring more informative PK data than plasma (see anticancer,
immunosuppresive or antiretroviral drugs).
Hope this help
Henri BENECH
CEA, France
email: henri.benech.-at-.cea.fr
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The following message was posted to: PharmPK
Hi Paul
>"My second question is that it seems to me that serum levels are
favoured for >monitoring of drug levels. Why do we use serum instead
of plasma or blood ? >or have i got the wrong end of the stick ? In
fact does it actually matter >whether a PK study uses blood levels
instead of plasma or serum levels."
AFAIK serum is generally preferred simply because it produces cleaner
extracts for sample quantification. However, there are various
reasons why other matrices, such as whole blood, should be collected
instead. A couple of examples are;
1) In cases where the drug molecules are highly associated with the
RBCs (such as with propofol) it may be preferable to collect whole
blood rather than plasma or serum.
2) Where it is important to minimise the sample handling time after
collection. For example, the synthetic opioid remifentanil is very
rapidly metabolised by plasma esterases. Hence remifentanil
concentrations are often quantified in whole blood so that the sample
can be frozen immediately after collection thus avoiding the loss of
remifentanil (due to metabolism) that may occur during sample
processing.
Best wishes
Ann
Dr Ann Rigby-Jones
Research Fellow
Anaesthesia Research Group, Peninsula Medical School,
Universities of Exeter & Plymouth, UK
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