Interventions for Tuberculosis Control and Elimination 2002

ifampicin, a peak level of 12 to 14 mg/L is achieved after one to three
hours (figure 13). 181,182 The AUC (between 0 and 12 hours) is 36 mg/L/hr,
and the half-life is estimated to be 4.7 (± 1.9) hours, 183 but has been found
to be shorter in three studies (3.8 to 4.1 hours) after a single dose of
10 mg/kg body weight. 175 A drug-concentration – time profile is shown
in figure 49. 175 Rifampicin is excreted unchanged in urine and bile and is
also metabolized. Its major metabolite, desacetyl-rifampicin, is excreted
principally in bile, but also in urine. 184 It appears that there are differences
between men and women in the blood levels achieved, with women
achieving significantly higher levels than men, a difference not explained
by differences in body weight. 185 The pharmacokinetics of rifampicin are
influenced by meals, 186,187 but depend on the type of constituents.
Carbohydrates and proteins seem to have virtually no influence, while a
fatty meal reduces serum concentrations considerably, as shown in four
groups of 35 patients each (figure 14). 188 The major differences in pharmacokinetics
following a meal include a reduced total amount absorbed
(area under the curve) and delayed achievement of peak serum levels. 175
Tissue penetration of rifampicin is excellent into cavity linings, lung
parenchyma and kidneys, with levels above the serum levels (figure 15). 175
Levels below the serum levels but well above the minimum inhibitory concentration
are achieved in pyogenic bone lesions and the pleura. Critical
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Figure 13. Pharmacokinetics of rifampicin in healthy volunteers. Reproduced
from 181 by the permission of the publisher ASM Press.