Drug properties

Plasma and urine levels of coproporphyrin I and coproporphyrin III could help detect drug-drug interactions involving SLCO1B1 and SLCO1B3. In a human cell line, overexpression of human SLCO1B1 or SLCO1B3 increased uptake of coproporphyrins I and III compared with normal SLCO1B1/1B3 expression. In the SLCO1B1/1B3-overexpressing cell line and in human hepatocytes, rifampicin - an inhibitor of SLCO1B1, SLCO1B3 and other organic anion transporter proteins - decreased uptake of coproporphyrins I and III compared with vehicle. In mice, knockout of SLCO1B1 and SLCO1B3 increased plasma and urine levels of coproporphyrins I and III compared with normal SLCO1B1/1B3 expression. In monkeys, rosuvastatin plus cyclosporin A - a combination with a known adverse drug-drug interaction - increased plasma and urine levels of the coproporphyrins compared with rosuvastatin alone. Next steps could include developing a test for measuring plasma or urine levels of the coproporphyrins for use in clinical trials.

The generic antibiotic rifampicin is marketed to treat tuberculosis...