COMPARISON OF BLOOD CONCENTRATION OF RIFAMPICIN BETWEEN ADMINISTRATION BEFORE AND AFTER BREAKFAST

Abstract

It is believed that blood level of rifampicin is higher when administered before meal than after meal, and rifampicin is being administered in general before breakfast. However, there is some difficulty in patients with far-advanced disease to give the drug before breakfast, as the patients may have gastric complaints. It is necessary to consider the value of adminis tration before meal, however, there is only one paper concerning with this problem based on the data of Japanese patients.
Rifampicin was administered at a single dose of 0.45g together with 0.75g ethambutol and 0.3g isoniazid. The latter two drugs proved to show no effect on the measurement of rifampicin concentration by biological assay. Rifampicin was administered 30 minutes before breakfast or 30 minutes after breakfast, and rifampicin concentration in blood was tested at 2, 4 and 6 hours by two different methods. The first was disc-agar diffusion method using Bacillus subtilis NRRL BSS8R as a test organism, and the second was serial 2-fold dilution method using Staphylococcus aureus 209 P as a test organism. Relationship between the values measured by both methods is shown in Figure 1. Although there is a considerable deviation in estimation, there is a correlation between the results obtained by these methods. In tables, the results estimated by the second method were given by using the index “x”= (log N/log 2), where N is a reciprocal of “minimal inhibitory serum dilution”.
1. Comparison of blood level of rifampicin between administration before and after break fast (Estimations on the same patients) Peak of blood level of rifampicin appeared to be not so significantly different from each other (Table 1). Peak appeared somewhat later when administered after meal. There is a significant difference in peak level from individual to individual. This individual variation seemed to be more important than the time of administration. The height of peak did not seem to be correlated with body weight.
2. Comparison of blood level of rifampicin between administration before and after break fast (Estimations on two groups divided by random allocation)
Nine patients were administered with 0.45 g rifampicin 30 minutes before breakfast and 8 patients 30 minutes after breakfast. Mean of peak values did not differ significantly (P>5%; “t”-test) by the time of administration. Peak of blood level appeared 2 hours after administration in the group administered before meal, whereas it appeared 4 hours after administration in the group administered after meal (Table 2 and Figure 2).
There is no significant difference between male and female in respect to the height of peak (Table 3).