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HI ALL,
During calculation of bioavalabiity of Cefepime administered via IM route, it is found more than 100%. So how this correction of possible error in calculation of availability is done?
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Hi,
You need to provide more information if you are asking for help. What is the value for bioavailability you get after the IM route? Are we talking 101% vs. 100% or is it a much larger difference? How many subjects were included in your study? Was this a parallel study, where they received the dose twice, once as IV and once IM? Was there any differences in the Cmax values between the two administrations? How much of your AUC is extrapolated after each dose? By extrapolation I mean the ratio of AUCt-infinity over the total AUC.
Many times, the IM administration results in a flip-flop situation, where you get prolonged absorption that changes the concentration-time profile of a drug, extending it beyond the sampling window and resulting in a large part of the AUC being extrapolated. This may cause issues, including what you describe.
So, provide some more information and hopefully somebody will be able to help you.
Toufigh
Toufigh Gordi, PhD
Clinical Pharmacology, PK/PD analysis consultant
www.tgordi.com
E-mail: tg.-a-.tgordi.com
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Hi Dear,
The value of bioavailability by IM route is 160 %. Six animals are included in my study. This study is parallel. I have calculated bioavailability by AUC (IM) divided by AUC(IV).
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It is possible a result of the enterohepatic circulation and re-absorption of your compound, if first pass is not significant, it might impact the %F value
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Do you use the same dose for IV and IM routes? If not, the F% larger than 100% is a very common phenomenon.
Jian
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Dear Nilesh,
The value of F should not be greater than the IV, please kindly let me
know the following points....1) Is your sample were analyzed on the
same day with same linearity if not then please kindly check the area
of the linearity curve whether its matching with what you have used
for calculation of IV and IM samples. Because if you extrapolate your
IM sample with the low concentration and considering it right then off
course the values what you are getting is more than the actual. So plz
check the linearity range , injection volume etc.
I hope this will solve the issue.
Regards,
Aslam Burhan
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I'm usually just an interested reader here, but is it true that the
assumption that F=1 for IV administration is an approximation, or is it
taken to be true by definition? I've seen it written that F=1 for
intra-arterial administration is a better approximation.
Scott Lett
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Any one calculating %F should always consider dose normalization!
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Yes i have used the same dose for IV and IM administration.
Are there any correction procedure after calculation of F?
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F greater than 1. Possible ppt of dose at the site of injection?
Stanley Cotler
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Nimesh,
Bioavailability more than 1 (more than 100%) is very common, not only in i.m. injections but also in oral administration.
This is of no surprise to me.
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 i.m. 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
K. W. WARD*, L. B. HARDY, J. R. KEHLER, L. M. AZZARANO and B. R. SMITH
Preclinical Drug Discovery, Cardiovascular & Urogenital Center of Excellence in Drug
Discovery, GlaxoSmithKline, King of Prussia, PA 19406, USA
regards,
vishal
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