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Dear Sir,
In the treatment of leprosy WHO recommends rifampicin
(600 mg once in month), clofazimine 300 mg booster
dose plus 50 mg daily, plus dapsone.
Clofazimine takes takes 70 days to reach therapeutic
conc. so a booster dose is given to take that into
account. Then what is the need for the another booster
dose of 300 mg every month when a 50 mg dose is given
daily. Can this be explained on the basis of
pharmacokinetics or some other reason is behind it.
looking forward to hear from you,
sincerely
jagdish
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Dear Jagdish:
Good question: I don't think so there was a pharmacokinetic basis for
booster dose of 300 mg. To best of my knowledge, clofazimine
half-life in human was not experimentally determined. Half-life was
predicted to be around 70 days. And there were several reports
published that clofazimine on multiple dose administration (for just
1 month of treatment)it will be deposited as crystals in various
reticuloendothelial tissue (lung, liver, spleen etc)in large amounts.
Still drug is non toxic. Sofar two or three metabolites were
identified, sulfate, glucuronide are predominant.
Sincerely
N.V.SRao Mamidi
Sr. Scientist
Drug Metabolism and Pharmacokinetics
Dr. Reddy's Research Foundation
Hyderabad.
India,
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Dear Dr Jaiswal,
The answer I believe lies not in the drug
levels,but in its dynamics.
Firstly the drug clofazamine has a preponderance for tissue binding,as a
result of which it causes discolouration of tissues.
Secondly in case of multi bacilliary leprosy,the dapsone resisant organisms
are not killed immediately but require at least a few weeks of therapy
before they are killed.
Hence by giving loading doses of clofazamine every month,these resistant
organisms are targeted, by building up adequate tissue levels of the drug
from which sites,the drug is released slowly.
Thank you for the interesting query,
Dr. Amit Taneja
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