Dear All
I performed a pk study of a molecule with iv, ip and sc routes of administrations. The Pk parameters showed high bioavailability of molecule in ip (>100%) and Sc (~200%). I checked the data repeatedly and ensured that all the values from bioanalysis and dosing regimens were fine. Can anyone provide your suggestions in this regard. As far as my understanding goes it could be delayed clearance of the compound!!!!. Kindly provide your views.
Regards
Pasha
Did you gave same dose for IV/IM/Sc?
Bioavailability more than 1 (more than 100%) is a common phenomena, not only in i.p. and Sc but also in oral administration. F greater than 1 is relative to i.v. administration and assuming that in any of the routes compared, Clearance does not change. This is a big assumption and many a times rate of elimination is controlled by rate of absorption. Thats what happens in im/ip/Sc. or sustained release dosages.
During regular NCE research it has been observed that with same vehicle when, an NCE was administered i.v. and orally, Fwas greater than 1.
This can be due to many reason.
Detailed investigation can be done as in following paper published in two parts. These papers are must read.
1. xenobiotica, april 2004, vol. 34, no. 4, 353-366
Apparent absolute oral bioavailability in excess of 100% for a vitronectin receptor antagonist (SB-265123) in rat. I. Investigation of potential experimental and mechanistic explanations
K. W. WARD*, L. M. AZZARANO, C. A. EVANS and B. R. SMITH
Preclinical Drug Discovery, Cardiovascular & Urogenital Center of Excellence in Drug
Discovery, GlaxoSmithKline, King of Prussia, PA 19406, USA
2. xenobiotica, april 2004, vol. 34, no. 4, 367-377
Apparent absolute oral bioavailability in excess of 100% for a vitronectin receptor antagonist (SB-265123) in rat. II. Studies implicating transporter-mediated intestinal secretion
Dear Masud
Thanks for the reply and also for the literature.
Regards
Khalid
If one uses models that do not estimate AUC properly, then unphysical results can follow. Such things as ip and sc routes require convolutional modelling of their corresponding iv bolus models. Using sums of exponential terms for iv will underestimate AUC. As a part fix you could try noncompartmental methods, but that has warts as well, that is, the extrapolations will still cause underestimation of AUC, just less so.
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