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Dear all,
where can I find the BCS class of newer drugs like alfulzosine,
nisoldipine. Is there any source.
With Kind Regards
Harshada.
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Dear Group Members,
Where can I find any officially publicized list of drugs classified
according to BCS and conditions their drug products should meet to be
approved for a biowaiver.
Best regards to all
Tanush KADRIA
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The following message was posted to: PharmPK
Dear Harshada,
Nisoldipine comes under BCS Class II drugs (high permeable, low
soluble).
For alfuzosin, as far as I know, there is no report on its BCS class.
But
the drug is highly lipophilic (Log P 1.61).
Prashant
--
Kole Prashant
Faculty,
Pharmacy Group,
Birla Institute of Technology and Science, Pilani.
Rajasthan, 333031
India
Phone: 01596-245074- ext - 458 [0ff]
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The following message was posted to: PharmPK
Dear Tanush,
Please refer to Draft Guidelines available on Biowaiver from World
Health
Organization.
Thanks,
Rakesh Chaurasia
Regulatory Pharmacist
Macleods Pharmaceuticals Ltd.
Mumbai-India
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The following message was posted to: PharmPK
Dear Prashant and Harshada,
The following experimental and estimated properties are a comparison
between Alfuzosin and Metoprolol:
Alfuzosin:
S+log D(7.4) = 1.89 (estimated using ADMET Predictor (AP),
Simulations Plus, Inc.)
Base pKa = 8.13 (Merck index)
Exlog P = 1.61 (experimental? as reported by Prashant)
S+IS = 0.438 mg/mL (intrinsic solubility using AP)
S+Peff = 0.27 x 10^-4 cm/s (human jejunal effective
permeability (Peff) from AP)
Dose number = 0.83 (Dose / Amt. dissolved in 250 mL water at
intrinsic solubility)
Dissolution number = 43.7 (mean SI transit time / mean
dissolution time)
Absorption number = 0.54 (mean SI transit time / mean
absorption time)
Metoprolol:
S+log D(7.4) = 0.26 (estimated from AP)
Base pKa = 9.7 (J. Pharm. Sci. 69(6):662 (1980)))
Exlog P = 1.88 (Biobyte Starlist)
S+IS = 9.2 mg/mL (intrinsic solubility using AP)
S+Peff = 0.94 x 10^-4 cm/s (human jejunal effective
permeability (Peff) from AP)
ExPeff = 1.3 x 10^-4 cm/s (experimental Peff Winiwarter S.,
J. Med. Chem. 41:4939 (1998)
Dose number = 0.0026 (Dose / Amt. dissolved in 250 mL water
at intrinsic solubility)
Dissolution number = 5x10^-3 (mean SI transit time / mean
dissolution time)
Absorption number = 1.88 (mean SI transit time / mean
absorption time)
As Prashant correctly points out, Alfuzosin is a lipophilic
molecule and according to (Kasim N.A., Molec. Biopharm. 1(1):85 2004,
"Molecular Properties of WHO Essential Drugs and
Provisional Biopharmaceutical Classification") having a log P less
than the log P for metoprolol would be sufficient to categorize the
molecule as being low permeability. However in this case the log P
values of Alfuzosin and Metoprolol are almost equal and by virtue of
its higher pKa metoprolol has a much lower distribution coefficient
at pH 7.4. Therefore, on the basis of log P or log D alone the
categorization of high or low permeability might be difficult.
However, permeability depends on more than just
lipophilicity. Hydrogen bonding is a key parameter in determining how
fast a molecule can passively cross through a biological membrane.
Alfuzosin (C19H27N5O4, Mwt. 389.46 g/mol) has five nitrogens and four
oxygens all of which can participate in H-bonding to the polar head
groups of a phospholipid bilayer. Even though Alfuzosin does not
break any of Lipinski's rules (> 5 HBD, > 500 MWt, > 5 log P, > 10 #
N and O) it does have an estimated human effective permeability that
is much lower than the experimental Peff for Metoprolol. The
Absorption Number (small intestinal transit time / small intestinal
absorption time) calculated by GastroPlus (Simulations Plus, Inc.) is
0.54 for Alfuzosin and 1.88 for Metoprolol. Therefore, the mean time
for absorption of Alfuzosin would be longer than the mean small
intestinal transit time. On the basis of the low estimated Peff and
low absorption number one would have to put Alfuzosin into the low
permeability class. The Dissolution Numbers and Dose Numbers for
Alfuzosin and Metoprolol would definitely put them both in the high
solubility category.
Taken all together I would say that Alfuzosin is Class III
(high solubility, low permeability).
Mike
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The following message was posted to: PharmPK
Dear Mike
As you rightly concluded Alfuzosin as Class III (high solubility, low
permeability) drug, which is also reflected in its in-vivo
pharmacokinetics.
It's very poorly absorbed under fasted condition (the extent of
absorption
is 50% lower under fasting conditions as compared to fed conditions) and
shows absolute bioavailability of 49 %. The Tmax is 8 hours and about
69% of
oral dose gets excreted in feces, indicating its poor absorption.
This all indicates its poor permeability
Additionally, it could also be substrate of intestinal P-glycoprotein
and
CYP3A4, indicating saturable absorption from small intestine.
Prashant
BITS, Pilani
--
Kole Prashant
Faculty,
Pharmacy Group,
Birla Institute of Technology and Science, Pilani.
Rajasthan, 333031
India
Phone: 01596-245074- ext - 458 [0ff]
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The following message was posted to: PharmPK
Pl. refer to the article
Classification of orally administered drugs on the World Health
Organization Model list of Essential Medicines according to the
biopharmaceutics classification system * REVIEW ARTICLE
European Journal of Pharmaceutics and Biopharmaceutics, Volume 58,
Issue 2, September 2004, Pages 265-278
Marc Lindenberg, Sabine Kopp and Jennifer B. Dressman
Rgds,
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Dear Prashant and Mike
Thanks for your quick reply and detailed explanation. But can you
provide me with the references. have you found that out after your
personal experimentation. I also wanted to know the classes for
Pramipexole, sibutramine, desloratidine and maxifloxacin.
Thanks and Regards
Harshada.
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)