Jume 5, 1961

Dr. Shigeichi Sunahara
Tokyo National Sanatoriunz
Tokyo, Japan

Dear Dr, Sunahara:

Thank you very much for sending me your very interesting monographs
on INH metabolise work performed in your laboratories. Enclosed you will
find reprints frem our own institution concerned with the subject.

My present belief is that rapid inactivators in our country receiving
TWH in our ‘¢ustomary 300 ag. dose do well enongh, especially when SM and
PAS are given with it, so that boosting the dose to very high levels makes
very little difference. “hen INH is given alone, however, the effect of
INH inactivation and dosage have been shown in Madras and in Fast ‘frica
te be important. While PAS does raise the serum concentration of free INH,
it does se to only a alight degree by our methods of analysis and does not
raise them as much aa can be achieved by moderate elevation of INH dosage.
In short, PAS acts with INH mostly: by its antibacterial activity rather
than its effect on INH metabolism, in my judgement, We must search for
means of detecting the wery rapid inactivator amongst all inactivators.
T have the impression t these occur in our population in about once in
50 or 100, These people have required up to 800 mg. in a single dose to
yleld 0.2 mog./ml. at 6 hours. ,

I hope ve may stay in correspondence with each other, and do pay
us a visit here in Denver when you can,

Sincerely yours,

RSM sch

Dr. Lederberg — / | |
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