Pharmacokinetic evaluation and relative bioavailability pilot study of fidaxomicin in healthy Chinese subjects: An open, randomized, single-dose, cross-over study.

Abstract

To compare the pharmacokinetic (PK) characteristics, investigate relative bioavailability, and provide data for potential additional bioequivalence trials between generic fidaxomicin (test (T) formulation) and the original brand (reference (R) formulation) in healthy Chinese subjects. An open, randomized, single-dose, cross-over study was conducted in 18 healthy Chinese subjects. The subjects randomly received T or R formulations and the alternative formulations were received after a 14-day wash-out period. Blood and fecal samples were collected and tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PK parameters were calculated using a non-compartmental model. Relative bioavailability considering commonly established bioequivalence criteria was assessed. Cmax were 3.58±2.74 ng/mL and 6.01±3.93 ng/mL, and AUC0-∞ were 35.71±18.68 h×ng/mL and 52.15±31.31 h×ng/mL for the T and R formulations, respectively. The tmax of both formulations was 5.00hours. The cumulative fecal excretion rate (Fe0-96h/F) of fidaxomicin and its main active metabolite OP-1118 were similar for both formulations. The geometric mean ratios and 90% confidence intervals (CI) of AUC0-t, AUC0-∞, and Cmax were not completely within the range of 80.00-125.00%. Significant within-subject and inter-subject coefficients of variation (> 30%) were found. Despite the differences in exposure, PK characteristics and fecal recovery of the two formulations were similar, suggesting that an effective concentration of the generic fidaxomicin could be achieved locally in the gastrointestinal tract. Fidaxomicin was a highly viable drug, thus providing reference for future clinical study design.