Assessing Food Effects on Oral Drug Absorption Based on the Degree of Renal Excretion
Tóm tắt
Food intake influences the pharmacokinetics of orally administered drugs by altering drug absorption, metabolism, and excretion. A drug which is mainly excreted into urine as parent drug is usually highly water-soluble and metabolically stable. Food intake is not expected to significantly affect its extent of oral absorption, metabolism, and excretion. Therefore, we hypothesize that an orally administered drug with significant renal excretion should not have a dramatic food effect (FE). To test our hypothesis, we summarized the FE for orally administered immediate-release (IR) and modified-release (MR) formulations approved by the US FDA from 1998 to 2019, focusing on drugs undergoing significant renal excretion. Totally, 98 active pharmaceutical ingredients (APIs) in IR formulations and 34 APIs in MR formulations were selected. The results demonstrate that the area-under-the-curve (AUC) for IR drug products with fur_unchanged_po > 10% is unlikely to be affected by food, although the peak plasma concentration (Cmax) may increase or decrease by up to 50%. Compared with IR drug products with fur_unchanged_po > 10%, MR drug products with fur_unchanged_po > 10% tend to have more significant FE. Although our proposed approach cannot substitute a clinical FE study, it could be a useful addition to early drug development to get an initial sense of the potential for FE for a drug candidate.
Tài liệu tham khảo
Lentz KA. Current methods for predicting human food effect. AAPS J. 2008;10(2):282–8.
Assessing the Effects of Food on Drugs in INDs and NDAs—clinical pharmacology considerations. In.: U.S. Food and Drug Administration; 2019.
Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12(3):413–20.
Wu CY, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res. 2005;22(1):11–23.
Benet LZ, Broccatelli F, Oprea TI. BDDCS applied to over 900 drugs. AAPS J. 2011;13(4):519–47.
Benet LZ. The role of BCS (biopharmaceutics classification system) and BDDCS (biopharmaceutics drug disposition classification system) in drug development. J Pharm Sci. 2013;102(1):34–42.
Dressman JB, Reppas C. In vitro-in vivo correlations for lipophilic, poorly water-soluble drugs. Eur J Pharm Sci. 2000;11(Suppl 2):S73–80.
Tistaert C, Heimbach T, Xia B, Parrott N, Samant TS, Kesisoglou F. Food effect projections via physiologically based pharmacokinetic modeling: predictive case studies. J Pharm Sci. 2019;108(1):592–602.
Rose RH, Turner DB, Neuhoff S, Jamei M. Incorporation of the time-varying postprandial increase in splanchnic blood flow into a PBPK model to predict the effect of food on the pharmacokinetics of orally administered high-extraction drugs. AAPS J. 2017;19(4):1205–17.
Li M, Zhao P, Pan Y, Wagner C. Predictive performance of physiologically based pharmacokinetic models for the effect of food on oral drug absorption: current status. CPT Pharmacometrics Syst Pharmacol. 2018;7(2):82–9.
Lakshmana Prabu S, Suriyaprakash TNK, Ruckmani K, Thirumurugan R. Basic pharmacokinetic concepts and some clinical applications. In; 2015.
Koziolek M, Alcaro S, Augustijns P, Basit AW, Grimm M, Hens B, et al. The mechanisms of pharmacokinetic food-drug interactions—a perspective from the UNGAP group. Eur J Pharm Sci. 2019;134:31–59.
BINOSTO DF. Drugs@FDA: FDA Approved Drug Products. FDA. 2019 Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202344s011lbl.pdf.
FOSAMAX DF. Drugs@FDA: FDA Approved Drug Products. FDA. 2019 Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021575s017lbl.pdf.
GALAFOLD DF. Drugs@FDA: FDA Approved Drug Products. FDA. 2019 Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=208623.
GRALISE DF. Drugs@FDA: FDA Approved Drug Products. GRALISE. FDA. 2019 Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022544.
NEURONTIN DF. Drugs@FDA: FDA Approved Drug Products. NEURONTIN. FDA. 2019 Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-397.pdf_Neurontin_Prntlbl.pdf.
Administration. USDoHaHSFaD. Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. Guidance for Industry. In. U.S. Department of Health and Human Services. Food and Drug Administration.; 2017.
Heimbach T, Xia B, Lin TH, He H. Case studies for practical food effect assessments across BCS/BDDCS class compounds using in silico, in vitro, and preclinical in vivo data. AAPS J. 2013;15(1):143–58.
Gu CH, Li H, Levons J, Lentz K, Gandhi RB, Raghavan K, et al. Predicting effect of food on extent of drug absorption based on physicochemical properties. Pharm Res. 2007;24(6):1118–30.
Deng J, Zhu X, Chen Z, Fan CH, Kwan HS, Wong CH, et al. A review of food-drug interactions on oral drug absorption. Drugs. 2017;77(17):1833–55.