Influence of food on pharmacokinetics and pharmacodynamics of furosemide.

Shibuta, Tatsuyuki; Inotsume, Nobuo; Iwaoku, Reiko; Nakano, Masahiro

doi:10.5649/jjphcs1975.14.12

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“…Thus, based on the Henderson–Hasselbalch equation, thermodynamic solubility of the drug is expected to be lower at pH 5.0 than at pH 6.5. The solubility ratio of furosemide between FeSSIF (684 μg/mL) and FaSSIF (3201 μg/mL) was reported to be 0.21 and that agrees with the negative food effect reported in the clinic [ 32 ]. It has been reported that the mucus layer present at the surface of the intestinal lining is associated with the lower microclimate pH than that of bulk phase in the intestine.…”

Section: Resultssupporting

confidence: 83%

Food effect risk assessment in preformulation stage using material sparing µFLUX methodology

2022

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The intake of food and meal type can strongly impact the bioavailability of orally administered drugs and can consequently impact drug efficacy and safety. During the early stages of drug development, only a small amount of drug substance is available, and the solubility difference between fasted state simulated intestinal fluid and fed state simulated intestinal fluid may provide an early indication about the probable food effect. But higher drug solubility in fed state simulated intestinal fluid may not always results in an increased oral absorption. In the present research, we demonstrated using 11 model compounds that in addition to the drug dissolution in biorelevant media, the evaluation of the diffusion flux of a drug in solution, across artificial lipid coated membrane, where only the unbound drug crosses the membrane, is a reliable way to predict the food effect. Although, the combination of dissolution and diffusion flux may not reliably predict the food effect in case of drugs undergoing intestinal metabolism or when transporters are involved in the drug absorption, the technique generally provides good information about the food effect at very early stages of drug development that may help in designing a clinical plan by adjusting the drug dose in the fed state.

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Section: Resultssupporting

confidence: 83%