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Dear Sir:
Nearly I investigated the pharmacokinetics of a new antibiotic agent
after intravenous (IV), intraperitoneal (IP), or intramuscularly (IM)
administration, and then calculated the corresponding pharmacokinetic
parameters. When a manuscript submitted to a journal, the comment was confused
me like this: "it is not necessary to calculate the apparent volume of
distribution and clearance for extra-vascular administration routes since they
are very influenced by the absorption phase. For the purpose of this study, it
is enough IV Vd and Cl values".
Am I wrong? If there anyone who would like to share your precious advice?
Thank you very much!
Best wishes!
Longshan Zhao
Shenyang Pharmaceutical University
[The V and CL determined from IP and IM would include F for each route of administration
and thus wouldn't need to be calculated. Reporting the IV parameters V and CL plus the F for each
route would be better. Alternately V and CL could be reported as V/F and CL/F for each route. - db]
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Dear Zhao,
For parameters like Vd and Cl should be calculated after intravenous
administration. Data obtained from other routes of administration could be
misleading.
I am agree with the comments given by reviewer.
Regards,
Rahul Vats
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The following message was posted to: PharmPK
Most accurate value of Vd and CL are obtained after intravenous administration.
After IP, I'm or PO administration one gets the apparent values, Vd/F or CL/F
where F is the fraction of the dose reaching systemic circulation. For IV
administration, F = 1.
Hope this helps.
Aziz Karim
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The following message was posted to: PharmPK
Dear Zhao,
The parameters obtained after IP or IM administration are the apparent volume of
distribution (Vd/F) and apparent clearance (CL/F).
Yes, since you had the IV data, you can directly get the CL and VD from that.
However, the Vd/F and CL/F are by no ways misleading as long as you qualify them
as the apparent volume and clearance. This is because these parameters are
assuming that the bioavailability (F)is 1. If F was less than 1, your parameters
would be higher. As a check, you calculate the bio-availability after IM and IP
dosing relative to the IV dose and use this F to determine the true CL and Vd
after IM and IP dose (CL = CL/F * F) . See if these values compare to the IV
values.
With respect to the volume of distribution and clearance for extra-vascular
administration routes being influenced by the absorption phase, in my opinion,
the absorption will affect the rate of elimination (only if absorption is slower
than elimination) and not the CL or volume. This can be seen if the half-life of
elimination is different between the IV and extra-vascular routes.
Hope this helps,
SA.
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The following message was posted to: PharmPK
Dear Dr Zhao,
As told from many collegues after ip or oral amministration you may calcolate
the apparent Vd (Vd/F) and clearance (CL/F), these to parmaters do not add value
to your paper, having already calculated the CL and Vd from iv dosing. However,
you may calculate the absolute bioavailability (F) after ip or oral dosing from
your data, and this add information about your drug.
Regards
Silvia Pace
Adme/PK
sigma-tau ifr SPA
Rome Italy
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