Population pharmacokinetic (PPK) analysis of recombinant human Apo2L/TRAIL (rhApo2L/TRAIL) in a Phase 1a Study in advanced cancer and lymphoma

Establishing combination PAC‐1 and TRAIL regimens for treating ovarian cancer based on patient‐specific pharmacokinetic profiles using in silico clinical trials

“…Individual patient clearance $$CL$$ and $$Vd$$ for PAC‐1 were then sampled from a multivariate normal distribution of these two parameters (Figure 2C). Similarly, the total body clearance and volume of distribution ($${\widehat {CL}_{TRAIL}} = 116$$ and variance $${{{\sigma}}_{TRAIL}} = 0.315$$, and $${\widehat {Vd}_{TRAIL}} = 4.28$$ and $${{{\sigma}}_{{\rm{TRAIL}}}} = 0.301$$ [34]) were used to define individual patient clearance and volume distribution values for TRAIL (Figure 2C). All parameter samples were restricted to being non‐negative.…”

Establishing combination PAC-1 and TRAIL regimens for treating ovarian cancer based on patient-specific pharmacokinetic profiles using in silico clinical trials

“…Individual patient clearance CL and Vd for PAC-1 were then sampled from a multivariate normal distribution of these two parameters ( Figure 2 C). Similarly, the total body clearance and volume of distribution ( and variance σ TRAIL = 0.315, and and σ TRAIL = 0.301 33 ) were used to define individual patient clearance and volume distribution values for TRAIL ( Figure 2 C). All parameter samples were restricted to being non-negative.…”

Death receptors as targets in cancer

“…Dulanermin's plasmatic concentrations were found to be compatible with most preclinical studies, ranging from 5 to 220 μg·mL −1 at 0.5 and 30 mg·kg −1 administration doses respectively. Pharmacokinetic parameters are not influenced by gender, race or enzymatic activities such as alkaline phosphatase or aspartate aminotransferase (Xin et al ., ). The half‐life of dulanermin, however, is relatively short and does not exceed 1 h, with no apparent accumulation in the serum (Herbst et al ., 2010a).…”