1578. Rifampicin Reduces Tedizolid Concentrations When Co-Administered in Healthy Volunteers

Abstract

BackgroundTedizolid is an oxazolidinone used to treat skin and soft-tissue infections. Rifampicin is a rifamycin antibiotic which can also treat skin and soft-tissue infections, such as those caused by Staphylococcus aureus. Tedizolid and rifampicin could be therefore used concurrently to treat infections. There is currently no clinical data on whether rifampicin affects tedizolid concentrations. Rifampicin is known to be an inducer of cytochrome P450s and transporters. Tedizolid is not known to be cleared by cytochrome P450s, but could be affected by other clearance mechanisms. Therefore we conducted a pharmacokinetic drug-drug interaction study to investigate whether 2 weeks of rifampicin can affect tedizolid concentrations.MethodsWe conducted a healthy volunteer study in 8 subjects. Subjects were first given linezolid 600 mg on day 1, tedizolid 200 mg on day 4, rifampicin 600 mg daily from days 5 to 19 (2 weeks of rifampicin), and an additional dose of tedizolid 200 mg on day 19. Blood was obtained at pre-dose, 1, 2, 3, 4, 5, 6, 8, and 24 hours post dose on days 4 and 19. Concentrations of tedizolid were measured using a validated liquid chromatography / mass spectrometry method.Pharmacokinetic parameters were calculated by Non-Compartmental Analyses using Phoenix WinNonLin version 8.0. The bioequivalence module was used to obtain ratios of PK parameters pre- and post-rifampicin.ResultsEight subjects were included in the study. Median age (range) and weight were 34.5 (29–44) years and 64 (58.4–90.8) kg, respectively. Tedizolid was well tolerated in the study. Tedizolid AUC (0–24 hours) was reduced after 2 weeks of rifampicin (GMR 0.80, 90% confidence interval 0.73–0.88), as was Cmin (0.54, 0.44–0.66) and Cmax (0.85, 0.79–0.91). Clearance/F of tedizolid was significantly increased after rifampicin (1.35, 1.21–1.50).ConclusionRifampicin given for 2 weeks has the potential to reduce tedizolid concentrations, especially trough levels, which was reduced by 46%. Caution is recommended when using tedizolid together with rifampicin, especially when tedizolid MIC is high or treating difficult infections.Disclosures All authors: No reported disclosures.