Studies of the metabolism of Isoniazid by Hughs, indicated a significant difference in
the metabolic fate of this drug in different subjects.
Another author has given evidence which suggests that the result of treatment with
Isoniazid in patients with pulmonary tuberculosis may depena upon the concentration of
biologically active drug in the blood. In addition, the demonstration of a high incidence
of rapid inactivators among persons of Japanese descent has provided anther means of
investigating the significance of biologically active Isoniazid serum concentration in the
treatment of tuberculosis.
The present study was undertaken to estimate the metabolic pattern of Isoniazid in
the people of Korea, as compared to the concentration of biologically active Isoniazid in
the blood from other non oriental groups.
121 person were studied ; 96 were patients with pulmonary tuberculosis, ranging in
age from six to seventeen. 25 were a group of healthy adults made up of doctors,
nurses and employees.
The method is a slight modification of that used by Bell and his associates, and is as
follows.
1) Youmans modification of Proskaur & Beck liquid medium was used.
2) Individual tubercle bacilli solution of H37 Rv. strain was made as follows ;
Colonies were crushed in a tube with liquid media and were centrifuged for 10
minutes at 1,000 r.p.m and then were centrifuged again, and the supernate fluid was
used as the solution of bacteria.
3) Then 0.1 ㎖ of bacilli solution were inoculated in the media in each tube with
graded concentrations of Isoniazid and were incubated for three days.
4) From the above culture, stained smears were made.
5) Inhibition of growth is determined microscopically on the stained smear by the
change in the size of the tubercle bacillis.
Inhibited bacilli were remained in their initial size in good contrast with growing
bacilli which were markedly increase in their size.
6) The determination of serum Isoniazid concentration if performed by comparing the
highest dilution of serum inhibiting growth with the minimum inhibiting concentration of
Isoniazid in the control tube.
The result are shown in Fig. 1
The great majority of people of Korean descent are rapid inactivators, as high as
72.7%, Therefore most tuberculous patients of Korean descent are expected to have
serum concentrations of free Isoniazid below the "optimal" range A clinical and
bacteriolocial response significantly less than that described in American patients would
be anticipated in Korean patients with pulmonary tuberculosis treated on drug regimens
utilizing conventional doses of 4-5 mgm perkilograms, Bases on the estimation of
Isoniazid blood levels, it is felt that a dosage of Isoniazid higher than conventional
recommended amounts is required in the treatment of pulmonary tuberculosis in this
specific racial group, the Korean people.
|