Whole-Body Physiologically Based Pharmacokinetic Modeling of Trastuzumab and Prediction of Human Pharmacokinetics.

In the present study, we evaluated the pharmacokinetics (PK) of trastuzumab and sought to predict human PK based on animal studies, through the use of optical imaging and a whole-body physiologically based pharmacokinetic (WB-PBPK) modeling approach. The PK study was conducted in 24 mice, where serial blood samples were withdrawn and major organs were isolated after the last blood withdrawal. The drug concentrations in blood and major organs were measured via optical imaging.

Prediction of the human antiplatelet effect of S- and R-indobufen using population pharmacodynamic modeling and simulation based on platelet aggregation test.

Indobufen (Ibustrin®), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using NONMEM® and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0-128 mg/L.

Postgastrectomy pharmacokinetic changes of S-1 in patients with localized advanced gastric cancer.

S-1 is an oral 5-fluorouracil agent containing tegafur, 5-chloro-2, 4-dihydroxypyridine (CDHP), and potassium oxonate. This study explored the pharmacokinetics of S-1 and pharmacokinetic changes after gastric surgery in patients with resectable gastric cancer who received pre- and postoperative S-1 plus docetaxel. Serial blood was drawn before and after gastrectomy from 37 patients for pharmacokinetic analysis.

Predicting the efficacy of an oral paclitaxel formulation (DHP107) through modeling and simulation.

Purpose: DHP107 is an oral paclitaxel under development. The present study characterized the pharmacokinetic properties of DHP107 and predicted the efficacy in comparison to that of intravenous paclitaxel, using modeling and simulation of data from the early phase of clinical development.

Methods: In the first-in-human study of the pharmacokinetic characteristics of DHP107 and intravenous paclitaxel, patients received DHP107 60 to 600 mg/m(2), followed by intravenous paclitaxel 175 mg/m(2).

Tolerability and pharmacokinetics of avanafil, a phosphodiesterase type 5 inhibitor: a single- and multiple-dose, double-blind, randomized, placebo-controlled, dose-escalation study in healthy Korean male volunteers.

Background: Avanafil is a selective phosphodiesterase type 5 inhibitor being developed for the treatment of erectile dysfunction.

Objective: This study was conducted to meet Korean regulatory requirements for the marketing of avanafil. To this end, tolerability and pharmacokinetic properties of single and multiple oral doses of avanafil in healthy Korean male volunteers were assessed.