Figure 7: Pharmacokinetic profiles of SC81458 and SC83288.
From: SC83288 is a clinical development candidate for the treatment of severe malaria
(a,b) Mean plasma concentration of SC81458 (a) and SC83288 (b) over time following i.p. administration of the indicated doses in mice. (c) Mean plasma concentration of SC83288 over time following i.v. administration of 2 mg kg−1 in monkeys (closed circles), mice (open circles), and rats (closed inverted triangles) and of 1.7 mg kg−1 in dogs (open triangles). For comparative reasons, the SC83288 AUC of the i.p. 10 mg kg−1 treatment group in mice is indicated in grey. The dotted lines show the lower limit of quantification (LLoQ). The mean±s.e.m. are shown for at least three animals. Data were examined using a non-compartment analysis (NCA) and relevant PK parameters are compiled in Table 2. (d) Four species allometric scaling of the plasma clearance rate (CL) of SC83288, according to Ring et al.30. The CL values were corrected for the maximum life potential (MLP). The function y=axb was fitted to the data points, yielding values for a of 9.47 and b of 1.17 (R2=0.997). Extrapolation of the fit provided estimates of the human blood clearance rate (red circle).
