The Pharmacokinetics of Gefitinib in a Chinese Cancer Population Group: A Virtual Clinical Trials Population Study

The Application of Virtual Therapeutic Drug Monitoring to Assess the Pharmacokinetics of Imatinib in a Chinese Cancer Population Group

“…85 In this study, we utilised virtual-TDM to optimise imatinib therapy in virtual Chinese and Caucasian cancer subjects. The imatinib model was adapted and validated in single and multiple dose studies in Caucasian subjects 19,[56][57][58] in addition to a being validated using a previously developed virtual Chinese cancer population group 60 with CML/GIST multiple dose studies. [61][62][63][64] In these validation studies, the predicted imatinib plasma concentrations were within the range reported in clinical studies (Fig.…”

“…In order to assess differences in pharmacokinetics of imatinib in Chinese and Caucasian cancer subjects, we utilised a previously developed virtual Chinese cancer population group 60 in a virtual trial to compare predicted trough imatinib plasma concentration to those reported at steady state for doses of (i) 100, 200, 250, 300, 400, 600 and 800 mg once daily (36 subjects aged 17-79 years); 61 (ii) 190 GIST subjects dosed at 400 mg once daily (31-85 years) demarked for age/ weight in addition to trough concentrations reported at doses of 300, 400, 500 and 600 mg once daily; 62 (iii) 84 CML subjects dosed 300-600 mg once daily (18-76 years); 63 (iv) 129 GIST subjects dosed 200-600 mg once daily (29-75 years). 64 This virtual Chinese cancer population group incorporates physiological alterations previously reported 35 to occur within oncology populations includes reductions in haematocrit, increases a-1 acid glycoprotein and decreases in both albumin and GFR.…”

“…C max or C min ) were compared with observed values and the standard deviation ratio (SDratio) calculated (Eq. ( 3)) 51 as follows:…”

“…49,50 Given the physiological difference between Chinese and Caucasian cancer patients, particularly changes in alpha-1-acid glycoprotein, the assessment of optimal doses to attain targeted plasma concentrations is warranted and can be pragmatically achieved through the use of mechanistic physiologically-based pharmacokinetic modelling approaches. 51 In this study, we utilise previous work conducted by our group to assess the requirements and approaches towards dose titrations in Chinese cancer patients, with explicit account of the physiological differences encountered in Chinese cancer patients compared to Caucasian cancer patients.…”

Virtual Clinical Trials Guided Design of an Age-Appropriate Formulation and Dosing Strategy of Nifedipine for Paediatric Use

“…A range of software companies offers PBPK modelling platforms [ 25 ], including paediatrics, of which the Simcyp™ Simulator is widely used to predict drug performance from virtual population groups, including paediatrics [ 26 , 27 ], pregnancy [ 28 , 29 , 30 ] and specialised disease states such as oncology [ 31 , 32 ].…”