Fig. 4: Plasma and urine pharmacokinetics of BWC0977 following 2-hr intravenous administration in the single-ascending dose (SAD) study in healthy human volunteers. Modelling and prediction of human PK parameters based on experimental data from preclinical species.
From: BWC0977, a broad-spectrum antibacterial clinical candidate to treat multidrug resistant infections
The PK of BWC0977 administered as a single intravenous infusion at doses 120, 240, 480, 720 or 1050 mg in healthy volunteers (n = 6 per dose) over 120 min. A The time-concentration response in plasma observed in the ascending dose groups. Mean ± SD from 6 subjects plotted versus time. B Dose proportionality observed with respect to plasma Cmax and AUC. Mean ± SD from 6 subjects plotted versus dose (mgs). (C) The amount of drug excreted in urine in the 48 h interval following dose administration was less than dose proportional to increasing dose, with the fraction of dose excreted in urine gradually decreasing from 35% for 120 mg BWC0977 to 20% for 1050 mg BWC0977. Mean ± SD from 6 subjects plotted versus dose (mgs). A model built on simple allometric scaling was used to predict the human PK parameters: Cmax (D) & AUC (E) based on a 2-compartment open model. Mean ± SD from 6 subjects plotted for each observed parameter. This was the best-fit model of the mean PK data generated following intravenous bolus / infusion administration of different doses of BWC0977 into mice, rats, guinea pigs and dogs. There was good concordance between the predicted and observed parameters.
