Tissue Distribution of ¹⁴C‐Rifampicin II. Accumulation in Melanin‐containing Structures

Abstract

Abstrucf:The tissue distribution of 14C-rifampicin was investigated by whole body autoradiography in brown mice surviving up to 30 days after a single intravenous injection. In contrast to the findings in albino mice a long-term retention was observed in the uveal tract, the inner ear and the skin. Similar results were obtained in pigmented rats. Sections of organs from a human foetus incubated in 14C-rifampicin showed selective accumulation in the pigment epithelium of the eye. Quantitative determinations of radioactivity were performed of the blood, liver, lung, kidney and eye of mice up to 4 days after a single intravenous injection of 14C-rifampicin. A 15-fold difference was found between the pigmented and the albino eye after 4 days. The findings were interpreted as evidence for a melanin affinity of rifampicin and discussed in relation to its possible ocular and otological side effects, which seem to be mostly unverified and very infrequent even during long-term therapy. However, the accumulation of transplacentally transferred drug in the eye and the inner ear provides a further reason for restricting its use during pregnancy.

Radiosynthesis and Bioimaging of the Tuberculosis Chemotherapeutics Isoniazid, Rifampicin and Pyrazinamide in Baboons

“…In the latter experiment, the liver still had the highest concentration (60.41 μg/g), while the heart, lung, and kidney retained some drug (10.11, 8.32, and 14.69 μg/g, respectively) . Finally, a semiquantitative evaluation of whole body RIF distribution in mice using iv injected [ 14 C]RIF suggested a similar drug distribution compared to our own studies except that the difference between the liver and other organs was not as large …”

“…19 Finally, a semiquantitative evaluation of whole body RIF distribution in mice using iv injected [ 14 C]RIF suggested a similar drug distribution compared to our own studies except that the difference between the liver and other organs was not as large. 33 The tissue distribution of injected [ 11 C]INH is shown in Figure 3 where it is clear that INH and/or its radiolabeled Article metabolites rapidly penetrates the heart, lung, liver, and kidney. Table 3 gives the estimated concentration of INH in μg/mL at 15, 30, 60, and 90 min following iv administration based on the recommended dose of INH, the weight of the baboon, and assumption that the positron signal derives primarily from the intact drug.…”

Tissue Distribution of 14C‐Rifampicin I. Whole Body Autoradiography of Albino Mice

“…Studies in pigmented animals could give further information on possible affinity to melanin and such a study will be presented in a subsequent paper (BOMAN 1975). Studies in pigmented animals could give further information on possible affinity to melanin and such a study will be presented in a subsequent paper (BOMAN 1975).…”