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Is it possible to get two different CL values for a drug when it is
given by iv bolus and by iv infusion? In other words, can the PK
parameters such as CL and Vd change during iv infusion? I have a
compound which when given by iv infusion gave a CL value that was 70%
less than the CL value from iv bolus. Is it possible?
Geo Thompson
Gnadakal5.aaa.yahoo.com
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Dear Geo Thompson
Concomitant saturation of renal and non-renal clearance might explain
this...
Similar results were discussed for (-)-carbovir earlier (CL
Zimmerman, PR 1991 8 739).
If clearance was saturated at high concentration of your compound
generated by IV bolus dose, clearance obtained after infusion will be
faster (as observed with Carbovir)
However, in your case the trend was reverse.
MRP1 transporter orientation in the lining of renal tubular
epithelial cells may explain your case.
Manthena Varma
Dr. Manthena VS Varma
NDDS-Pharmaceutical R&D,
Nicholas Piramal Research Center,
1, Nirlon Complex, Off Western Express Highway,
Near NSE Complex, Goregaon (E),
Mumbai-400 063, INDIA.
email: varma_mvs.-at-.yahoo.com or vmanthena.-at-.nicholaspiramal.co.in
Phone: +91 22 3081 8914; +91 932 426 9193
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Geo,
If your drug has a distribution phase that is not captured after
infusion but appears during the bolus administration, your volume
estimates may differ. Thus if you use the volume and elimination rate
constant to calculate clearance, it's value may turn out to be
different between the two routes of administration.
Pankaj Gupta
Virginia Commonwealth University
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Geo,
Assuming the drug in the dosing range follows linear
pharmacokinetics, by defination, clearance is the same. The
difference between clearance in your below example might originate
from your calculatioin method. You need to give more information
(e.g., how you calculated clearance.. etc) for people here to make a
suggestion of what exactly happened.
If the drug follows non-linear PK, nonliearity might help explain it.
PZ
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