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How do you explain a difference in the volume disribution (Vz)
following IV and IM administration for a drug given similar AUCs?
Khalid Alkharfy, Pharm.D., Ph.D.
Assistant Professor of Clinical Pharmaceutical Sciences
Department of Clinical Pharmacy
School of Pharmacy, KSU
PO Box 2457
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Dear Dr. Alkharfy,
I assume you are talking about the same dose given in both cases (IV &
In case of extravascular administration Vz represents Vz/F where F is
fraction absorbed. The same dose of drug administration by IV or IM resulting in
equal AUCs indicates 100% absorption after IM administration. In some
drugs, after IV adminsitration part of the drug is secreted back to the GIT and
reabsorbed (gastro-entero systemic recirculation). I think in your case also we
should check for any such mechanism is involved or not.
Hi,Back to the Top
I think that the difference in Vz between the IV and IM routes may be
due to the flip-flop phenomenon. Generally, in the IM kinetics, the
terminal rate constant (Kz) is similar to the Kz of IV when absorption
is not rate limiting and the Vz calculated should be similar to IV.
However, if absorption is rate limiting the Kz may represent the
absorption rate constant and so may be different from Kz of IV.
Therefore, this will alter the calculated Vz but will not alter the
AUC's. Thus, in this case the changes in calculated Vz may be due to
absorption rate limitation. I hope this will be helpful.
Texas Tech University Health Sciences Center
Amarillo, TX 79106
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