A new PBPK-DO simulation model can predict PK and PD profiles of trelagliptin and omarigliptin simultaneously in healthy humans.The PBPK-DO simulation model can predict the PK and PD profiles of trelagliptin and omarigliptin in patients with renal impairment.The PBPK-DO simulation model can provide more valuable recommendation about dosing adjustment in patient with renal impairment.A previous trial compared nab-paclitaxel with docetaxel for previously treated advanced non–small cell lung cancer.Safety and efficacy of nab-paclitaxel were here assessed for the trial patients with renal impairment.Nab-paclitaxel did not appear to exacerbate adverse events regardless of the level of renal impairment.Nab-paclitaxel is thus well tolerated and effective for such patients with renal impairment.Physiologically based pharmacokinetic models of janagliflozin were developed.Models were used to predict drug exposure changes in diabetic populations.Janagliflozin exposure was increased in T2DM populations with elevated cirrhosis severity.Risk benefit assessment is recommended for T2DM patients with cirrhosis.Models predicted stable pharmacokinetic profiles in T2DM populations with renal impairment.Janagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes mellitus (T2DM). The janagliflozin pharmacokinetics (PK) in T2DM patients with cirrhosis or renal impairment (RI) are unknown. To predict the janagliflozin PK in these patients, we constructed a physiologically based PK (PBPK) model that predicted the janagliflozin PK in normal animals. The model was extrapolated to healthy humans and optimized with the measured data.

A PBPK model for T2DM patients was developed and optimized with the measured data. Based on the physiological alterations in cirrhosis or RI patients, the T2DM model was applied to predict the janagliflozin PK in these patients. Results were validated using fold error values.  Child-Pugh-A, B, and C, respectively, and those in T2DM patients with RI-mild, RI-moderate, and RI-severe were 21,810, 21,840, and 22,845 ng/ml·h, respectively. Janagliflozin exposure increased with increasing cirrhosis severity, whereas it remained stable regardless of the RI severity. The PBPK model predicted the janagliflozin PK in patients with T2DM and liver cirrhosis or RI. Dose adjustment is less critical for these patients. Risk benefit assessment in janagliflozin dosing for T2DM patients with liver disease is recommended.

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Mishita
Jornal co-ordinator
Journal of Clinical & Experimental Nephrology