Dear All,Back to the Top
I would like to share a doubt ...
I could see that the new antibiotic from AstraZenica n rosuvastatin
(p.o) n has a bioavailability (F) of only 20%. So, it was a surprising
to me, because to oral administration drugs generally have F > 70 - 80
%. Sometimes drugs of same F (<20%) has the administration route
changed during drug development.
Could anyone discuss this point to me? Which is an adequate
bioavailability to an oral drug administration?
Thanks,
Daniel
The acceptable F factor is dependent on the drug toxicity to the GIBack to the Top
tract. Rapamycin is given orally with F less than 20%.
Also another common example (amongst many others) is oral morphine withBack to the Top
a systemic F of 20%-30%, due largely to an extensive first pass
metabolism as absorbed drug passes through the intestinal epithelium and
the liver.
Cheers
BC
Bruce CHARLES, PhD
Associate Professor and Director,
Australian Centre for Paediatric Pharmacokinetics
School of Pharmacy
The University of Queensland, 4072 Australia
[University Provider Number: 00025B]
TEL: +61 7 336 53194
FAX: +61 7 336 51688
B.Charles.aaa.pharmacy.uq.edu.au
http://www.uq.edu.au/pharmacy/brucecharles/charles.html
http://www.mater.org.au/pharm/accp.htm
Daniel, I do not think there is a set value for F, another good exampleBack to the Top
is saquinavir (protease inhibitor) that has an F value of less than
10%, resulting in huge daily dose (I think it is 3 x 400 mg/day).
Since saquinavir was one of the first in its class, this was acceptable
at the time and it sets the standard to beat from an oral
bioavailability standpoint. As far as F is concerned you have to weigh
the through concentration that you need to achieve and also the cost of
producing the material, with saquinavir keep in mind that 90% of the
material is not absorbed....and lost.
Jean-Pierre
Daniel,Back to the Top
There is no cut-ff figure for F, below which Oral route becomes
non-viable. It depends on the potency and pharmacokinetics of the drug.
For example Alendronate (Fosamax) used for treating Osteoporosis has
oral bioavailability of 0.64% only.!!!
Sunil Vandse
Able Labs
[Anyone know of a commercial product with a lower F, bowel
sterilization products excepted ;-) - db]
Saquinavir has reported bioavailability of 0.5-1.0%, approximatelyBack to the Top
doubling after grapefruit juice because of CYP3A4 reduction in the gut
wall. Absorption (across the apical membrane) is about 85%, but the gut
wall metabolizes about 80% of that, so the amount reaching the portal
vein is only about 15-20%, and after first pass hepatic extraction,
only about 0.5-1 % remains.
See: H.H. Kupferschmidt, K.E. Fattinger, H.R. Ha, F. Follath, S.
Krahenbuhl, Grapefruit juice enhances the bioavailability of the HIV
protease inhibitor saquinavir in man, Br. J. Clin. Pharmacol. 45 (1998)
355n359.
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (AMEX: SLP)
1220 W. Avenue J
Lancaster, CA 93534-2902
U.S.A.
http://www.simulations-plus.com
Phone: (661) 723-7723
FAX: (661) 723-5524
E-mail: walt.-at-.simulations-plus.com
Hi Walt,Back to the Top
May I have reference(s) of article(s) suggesting ~85% absorption for
saquinavir.
Thanks in advance.
Kasiram.
At 01:49 AM 5/7/2004, Kasiram Katneni wrote:Back to the Top
"May I have reference(s) of article(s) suggesting ~85% absorption for
saquinavir."
See:
Agoram, Woltosz, & Bolger - Predicting the impact of physiological and
biochemical processes on oral drug bioavailability, Adv Drug Deliv
Reviews 50 (2001) S41-S57.
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (AMEX: SLP)
1220 W. Avenue J
Lancaster, CA 93534-2902
U.S.A.
http://www.simulations-plus.com
Phone: (661) 723-7723
FAX: (661) 723-5524
E-mail: walt.-a-.simulations-plus.com
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