Tissue distribution of 14-C-rifampicin II. Accumulation in melanin-containing structures.

Abstract

Abstract: 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.