A prior model that showed good predictability for fed-state and fasted-state biorelevant media was extended to predict the degree to which fed-state biorelevant media (i.e. FeSSGF and FeSSIF-V2) enhanced drug dissolution over fasted-state biorelevant media (i.e. FaSSGF and FaSSIF-V2): ϕfood=vfast1/6vfed1/6·(ff,fedDD2/3+fm,fedDD−M,fed2/3)[Dt,fed](ff,fastDD2/3+fm,fastDD−M,fast2/3)[Dt,fast] where ϕfood is the degree by which fed-state biorelevant media enhanced in vitro drug dissolution over fasted state biorelevant media, ff,fast and ff,fed are the fraction of free drug in fasted and fed biorelevant media, fm,fast and fm,fed are the fraction of drug in fasted and fed mixed micelles (or fat globules in FeSSGF), DD is the free drug diffusivity, DD−M, fast and DD−M, fed are the fasted and fed mixed micelle (or fat globule) diffusivity, and [Dt,fast] and [Dt,fed] are the total drug solubilities in fasted and fed-state biorelevant media, respectively. Solubility, particle size measurement, and intrinsic dissolution studies were performed for model BCS Class II drugs griseofulvin, ketoconazole, and ibuprofen each in FaSSGF, FeSSGF, FaSSIF-V2, and FeSSIF-V2 to compare observed versus predicted dissolution enhancement in fed-state over fasted-state biorelevant media. Relative to solubilization, in vitro dissolution was many fold lower in fed media over fasted media, indicating the compromising role of micellar and fat-globule diffusivity in attenuating dissolution rate based on solubility enhancement alone. Results of ϕfood agreed with what was observed and were also corroborated by reported food effects in vivo for griseofulvin, ketoconazole, and ibuprofen. The understanding of attenuation of in vitro dissolution in fed versus fasted biorelevant media may contribute towards predicting in vivo food effects, including lack of in vivo food effect for some poorly water soluble drugs.