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I am just curious if anybody studied effect of hemolysis on the
bioanalytical results of a freely water soluble drug in plasma. I would like
to hear any comments.
Regards,
Prasad Tata
Mallinckrodt, Inc.
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Hi Prasad!
We should remember that red blood cells are - in vitro and in vivo - a
compartment of drug distribution.
If a drug is uniformly distributed throughout the blood, i.e. when drug
distribution/binding is similar in plasma and in blood cells, clearance
parameters determined from plasma concentrations are a good approximation of
the actual systemic clearance. When the drug distribution/binding in blood
cells exceeds binding in plasma, however, plasma clearance can overestimate
systemic clearance (the drug distribution constants are significantly higher
than drug reuptake constants).
So sometimes results from hemolysed samples are incorrectly interpreted as
an "improved drug recovery", while are only the result of the drug release
from an "inner compartment" to the plasma compartment.
Just an example on an anthracycline: epirubicin (a water freely soluble
drug).
We measured EPI in plasma and whole blood in 4 cancer patients. Drug
concentrations were 2-5 times higher if measured in whole blood rather than
in plasma and blood clearance was considerably lower than plasma clearance.
Conversely, MRT was similar whether measured in plasma or blood. Vss was
lower if blood concentration data were used in pharmacokinetic analysis.
In this case hemolysed samples are not comparable with non-hemolysed
samples.
Best regards
Elena Strocchi
Elena Strocchi
Laboratorio di Farmacocinetica ANT
Dipartimento di Chimica Organica
Universita' di Bologna
Viale Risorgimento, 4
40136 Bologna - Italy
e-mail: strocchi.at.ms.fci.unibo.it
WEB: //antlab.fci.unibo.it
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We studied the pharmacokinetics of sodium nitrite in blood for a
study on nitrite-induced methemogloinemia (Drug Metab. Disp. in
press). Treating the blood as a homogeneous compartment greatly
under-predicted the observed blood time courses and over-predicted
clearance. The solution to this problem was to partition the nitrite
between plasma and RBCs. The effective partition coefficient was very
high (> 12), suggesting active uptake by the erythrocytes.
Michael C. Kohn
Laboratory of Computational Biology and Risk Analysis
National Institute of Environmental Health Sciences
P.O. Box 12233, Mail Drop A3-06
Research Triangle Park, NC 27709-2233
E-mail: kohn.aaa.niehs.nih.gov (Work)
Web site: http://dir.niehs.nih.gov/dirlcbra/kohn
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