Table 3.

PBPK models in product labels or FDA review documents: Drug absorption

ID	NME	Year of approval	Detail of predicted scenarios	Simulation results	Impact / outcome	Referencesa
21	Alectinib	2015	Timing of food on alectinib exposureb	Less than 20% change predicted	PBPK model not reviewed because no obvious exposure‐response relationship identified	27450228
22	Ceritinib	2014	Food effect	Cmax change matched observation but AUC did not	No direct labeling impact, FDA exploratory simulations
			Effect of gastric pH change	Cmax and AUC decrease by 10%
			P‐gp contribution to intestinal absorption	Appeared to be minimal
23	Ibrutinib	2013	Food effect to explain different exposure between healthy and oncology subject	Pharmacokinetic differences ascribed to type and timing of food on hepatic/intestinal blood flow rate	No direct labeling impact
			Intestinal exposure prediction	Dose staggering could lower the risk of P‐gp‐mediated DDI
24	Naloxegol	2014	P‐gp contribution to intestinal absorption	Appeared to be minimal	No direct labeling impact	27299937
25	Panobinostat	2015	Effect of gastric pH changec	Minimal effect predicted (no change in the fraction of a drugs absorbed up to the gastric pH of 8.0)	Label states no ARA effect observed in simulation
26	Sonidegib	2015	Food effect	Significant underestimation compared to clinical data	No direct labeling impact, FDA exploratory simulations

ARA, acid reducing agents; AUC, area under the curve; C_max, peak plasma concentration; FDA, US Food and Drug Administration; ID, identification; NME, new molecular entity; PBPK, physiologically based pharmacokinetic; P‐gp, P‐glycoprotein.

^aThe numbers in the Reference column represent PubMed ID (if PBPK models were published in scientific journals). New drug application review documents can be found at Drugs@FDA (http://www.fda.gov/drugsatfda).

^bGastroPlus was used for PBPK simulation.

^cGastroPlus and Simcyp was used for PBPK simulation. If not specified, Simcyp was used for PBPK simulations.