Effect of Food Composition on the PK of Isoniazid Quantitatively Explained Using Physiologically Based Biopharmaceutics Modeling.

This work shows the utilization of a physiologically based biopharmaceutics model (PBBM) to mechanistically explain the impact of diverse food types on the pharmacokinetics (PK) of isoniazid (INH) and acetyl-isoniazid (Ac-INH). The model was established and validated using published PK profiles for INH along with a combination of measured and predicted values for the physico-chemical and biopharmaceutical propertied of INH and Ac-INH. A dedicated ontogeny model was developed for N-acetyltransferase 2 (NAT2) in human integrating Michaelis Menten parameters for this enzyme in the physiologically based pharmacokinetic (PBPK) model tissues and in the gut, to explain the pre-systemic and systemic metabolism of INH across different acetylator types. Additionally, a novel equation was proposed to calculate the luminal drug degradation related to the presence of reducing sugars, using individual sugar molar concentrations in the meal. By incorporating luminal degradation into the model, adjusting bile salt concentrations and gastric emptying according to food type and quantity, the PBBM was able to accurately predict the negative effect of carbohydrate-rich diets on the PK of INH.

Enriching the FIDEO ontology with food-drug interactions from online knowledge sources.

The increasing number of articles on adverse interactions that may occur when specific foods are consumed with certain drugs makes it difficult to keep up with the latest findings. Conflicting information is available in the scientific literature and specialized knowledge bases because interactions are described in an unstructured or semi-structured format. The FIDEO ontology aims to integrate and represent information about food-drug interactions in a structured way. This article reports on the new version of this ontology in which more than 1700 interactions are integrated from two online resources: DrugBank and Hedrine. These food-drug interactions have been represented in FIDEO in the form of precompiled concepts, each of which specifies both the food and the drug involved. Additionally, competency questions that can be answered are reviewed, and avenues for further enrichment are discussed.

Safety, Tolerability, and Pharmacokinetics of the Monoamine Oxidase B Inhibitor, HEC122505, and its Major Metabolite After Single- and Multiple- Ascending Dose, and Food Effect Study in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVES: HEC122505 is a potent and selectively monoamine oxidase B inhibitor that is safe and well-tolerated in preclinical models of Parkinson's disease. The objectives of single ascending dose and multiple dose pharmacokinetic trials of HEC122505 oral tablets were to determine the safety and tolerability of HEC122505, and to examine the food effect on the pharmacokinetic parameters of HEC122505 and its major metabolite HEC129870. METHODS: The phase I study (NCT04625361) consisted of three arms: single ascending dose study (5, 20, 50, 100, 200, 300 or 400 mg HEC122505 tablets or placebo), multiple ascending dose study (20, 50 or 100 mg HEC122505 tablets or placebo once daily), and food effect (100 mg HEC122505 tablets single dose after a high-fat, high-calorie meal). All subjects completed all trial arms and were analyzed as planned. RESULTS: Pharmacokinetic analysis showed that HEC122505 rapidly absorbed with the time to peak plasma concentration (Tmax) ranged from 0.5 to 1.75 h. In addition, maximum plasma drug concentration (Cmax) and area under the plasma concentration-time curve (AUC) increased in a dose proportional manner. Food effect study showed that a high-fat, high-calorie meal had no significant effect on the pharmacokinetics of HEC122505 and its major metabolite HEC129870, suggesting that HEC122505 could be administered in both fasted and fed state in clinical trials. The subsequent multiple-dose study evaluated doses from 20 to 100 mg dose once daily for up to 8 days. HEC122505 reached steady state after approximately 5 days with a once daily dose. In these studies, all dose of HEC122505 was generally safe and well tolerated. No grade ≥ 3 drug related adverse events (AEs) occurred. CONCLUSION: HEC122505 was generally safe and well tolerated in the single ascending dose (ranging from 5 to 400 mg) and multiple ascending dose (50 to 200 mg once daily doses) studies. All the drug related adverse events (AEs) were Grade ≤ 2. There were no deaths, no subjects discontinued the trial due to AEs, and there were no other serious AEs. The safety and pharmacokinetic profile support once daily administration of HEC122505.

Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies in Migraine: Focus on Drug Interactions.

Calcitonin gene-related peptide neurotransmission was the target for recent development of monoclonal antibodies that effectively prevent attacks of both episodic and chronic migraine. The aim of this narrative review was to offer deeper insight into drug-drug, drug-food and drug-disease interactions of monoclonal antibodies approved for prevention of migraine attacks. For this narrative review, relevant literature was searched for in MEDLINE and Google Scholar databases, covering the 1966-2023 and 2006-2023 periods, respectively. The ClinicalTrials.gov database was also searched for relevant clinical studies whose results had not been published previously in medical journals, covering 2000-2023. Monoclonal antibodies (erenumab, fremanezumab, galcanezumab and eptinezumab) augment prophylactic action of gepants and onabotulinumtoxin A and somewhat increase efficacy of triptans used to abort migraine attacks; however, their adverse reactions may also be augmented. Pharmacokinetic interactions and interactions in general with drugs used for other indications except migraine are negligible, as are drug-food interactions. However, monoclonal antibodies may worsen diseases with already weakened CGRP neurotransmission, Raynaud phenomenon and constipation. Monoclonal antibodies used for prevention of migraine do not engage in significant pharmacokinetic interactions with other drugs; however, they do engage in pharmacodynamic interactions with other anti-migraine drugs, additively augmenting their prophylactic action, but also increasing frequency and severity of adverse reactions, which are a consequence of the CGRP neurotransmission interruption.

Comparative Bioequivalence and Food Effect of Two Formulations of 30-mg Nifedipine Controlled-Release Tablets in Healthy Chinese Adults.

Nifedipine is a potent antihypertensive medication classified as a dihydropyridine calcium channel blocker. The objective of this trial was to assess the bioequivalence of a 30-mg nifedipine controlled-release tablet and a reference drug in a cohort of healthy Chinese individuals. Two independent open-label, randomized, single-dose, crossover studies were conducted, 1 under fasting conditions (N = 44, with 1 participant dropping out midway) and the other under fed conditions (N = 44, with 4 participants dropping out midway). Plasma concentrations of nifedipine were determined using liquid chromatography-mass spectrometry, and pharmacokinetic (PK) parameters were calculated using noncompartmental analysis with Phoenix WinNonlin 8.0 software. In both fasting and fed studies, reasonable bioequivalence was observed for the PK parameters of both the test product and the reference drug. A good safety profile was demonstrated for both the test product and reference drug, with no serious adverse events reported, and both were similarly well tolerated. An important observation with food coadministration was that systemic exposure to nifedipine (based on area under the curve, AUC0-∞) was reduced by approximately 12%. The bioequivalence of the test product and reference drug under fasting/fed conditions in healthy subjects in China was demonstrated by the study results.

Two-Part Phase 1 Study to Evaluate the Taste Profile of Novel Belumosudil Oral Suspensions and Assess the Relative Bioavailability and Food Effect of the Selected Belumosudil Oral Suspension Compared With Oral Tablet Reference in Healthy Male Participants.

Belumosudil is a selective rho-associated coiled-coil-containing protein kinase 2 inhibitor in clinical use for the treatment of chronic graft-versus-host disease. The current tablet formulation may be inappropriate for children or adults with dysphagia and/or upper gastrointestinal manifestations of chronic graft-versus-host disease. This study (NCT04735822) assessed the taste and palatability of oral suspensions of belumosudil, evaluated the relative bioavailability of an oral suspension versus the tablet formulation, and characterized the effect of food on the pharmacokinetics of an oral suspension. Addition of sweetener and/or flavor vehicle improved the taste. Relative bioavailability of 200-mg doses of the oral suspension and tablet in the fed state was similar for belumosudil and its metabolites (KD025m1 and KD025m2), but absorption was faster with the oral suspension (median time to maximum concentration: 2 vs 3 hours). Administration of the oral suspension with food increased exposure compared with fasted administration, with maximum observed concentration being increased by 16% and area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) by 19%. Safety and tolerability were consistent with the known safety profile of belumosudil. These results may support administration of a 200-mg belumosudil oral suspension with or without food.

Pharmacokinetic Evaluation of the CYP3A4 and CYP2C9 Drug-Drug Interaction of Avacopan in 2 Open-Label Studies in Healthy Participants.

Avacopan, a complement 5a receptor (C5aR) antagonist approved for treating severe active antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, was evaluated in 2 clinical drug-drug interaction studies. The studies assessed the impact of avacopan on the pharmacokinetics (PK) of CYP3A4 substrates midazolam and simvastatin and CYP2C9 substrate celecoxib, and the influence of CYP3A4 inhibitor itraconazole and inducer rifampin on the PKs of avacopan. The results indicated that twice-daily oral administration of 30 mg of avacopan increased the area under the curve (AUC) of midazolam by 1.81-fold and celecoxib by 1.15-fold when administered without food, and twice-daily oral administration of 30 or 60 mg of avacopan increased the AUC of simvastatin by approximately 2.6-3.5-fold and the AUC of the active metabolite ß-hydroxy-simvastatin acid by approximately 1.4-1.7-fold when co-administered with food. Furthermore, the AUC of avacopan increased by approximately 2.19-fold when co-administered with itraconazole and decreased by approximately 13.5-fold when co-administered with rifampin. These findings provide critical insights into the potential drug-drug interactions involving avacopan, which could have significant implications for patient care and treatment planning. (NCT06207682).

Enhancing drug-food interaction prediction with precision representations through multilevel self-supervised learning.

Drug-food interactions (DFIs) crucially impact patient safety and drug efficacy by modifying absorption, distribution, metabolism, and excretion. The application of deep learning for predicting DFIs is promising, yet the development of computational models remains in its early stages. This is mainly due to the complexity of food compounds, challenging dataset developers in acquiring comprehensive ingredient data, often resulting in incomplete or vague food component descriptions. DFI-MS tackles this issue by employing an accurate feature representation method alongside a refined computational model. It innovatively achieves a more precise characterization of food features, a previously daunting task in DFI research. This is accomplished through modules designed for perturbation interactions, feature alignment and domain separation, and inference feedback. These modules extract essential information from features, using a perturbation module and a feature interaction encoder to establish robust representations. The feature alignment and domain separation modules are particularly effective in managing data with diverse frequencies and characteristics. DFI-MS stands out as the first in its field to combine data augmentation, feature alignment, domain separation, and contrastive learning. The flexibility of the inference feedback module allows its application in various downstream tasks. Demonstrating exceptional performance across multiple datasets, DFI-MS represents a significant advancement in food presentations technology. Our code and data are available at https://github.com/kkkayle/DFI-MS.

Physiological, Anatomical and Physicochemical Characteristics of Children Affecting Food-Drug Interaction-Review.

The drug-food interaction has a great interest in nutrition research to minimize unfavorable reactions to nutritional treatment. Failure to supply appropriate nutrition to the child can harm both body development and growth. This review aimed to examine available data on the impact of diet on medication absorption in pediatric populations. Mechanisms underlying food-drug interactions were investigated to explore possible distinctions between adult and pediatric populations and to gain insight into how this may impact the pharmacokinetic profile in a child. Several changes in physiology, anatomy and physicochemical properties among children are likely to result in food-drug interactions that cannot be anticipated based on adult studies. The influence of food on medications results in decreased bioavailability and altered drug elimination. Drugs, on the other hand, can affect dietary intake, digestion, absorption and excretion. Literature shows that differences in gastrointestinal physiology and anatomy between pediatric and adult populations can have a major impact on drug absorption and bioavailability. A higher splanchnic blood flow may result in decreased drug bioavailability due to increased loss in first-pass metabolism. To overcome the overall lack of knowledge on analyzing food-drug interactions among pediatric populations, comprehensive procedures and recommendations must be developed.

Pharmacokinetics of Dasatinib in Rats: a Potential Food-Drug Interaction with Naringenin.

BACKGROUND AND OBJECTIVES: The novel tyrosine kinase inhibitor (TKI) dasatinib, a multitarget inhibitor of Bcr-Abl and Src family kinases, has been licensed for the treatment of Ph+ acute lymphoblastic leukemia and chronic myeloid leukemia. Many citrus-based foods include the flavonoid naringenin, which is commonly available. Dasatinib is a Cyp3a4, P-gp, and Bcrp1 substrate, which makes it sensitive to potential food-drug interactions. The concurrent use of naringenin may change the pharmacokinetics of dasatinib, which could result in adverse effects and toxicity. The present investigation examined the impact of naringenin on the pharmacokinetics interactions of DAS and proposes a possible interaction mechanism in Wistar rats. METHODS: Rats were provided with a single oral dose of dasatinib (25 mg/kg) with or without naringenin pretreatment (150 mg/kg p.o. daily for 7 days, n = 6 in each group). Dasatinib was quantified in plasma by UHPLC MS/MS assay. Noncompartmental analysis was used to compute the pharmacokinetic parameters, and immunoblot was used to assess the protein expression in the hepatic and intestinal tissues. RESULTS: Following 7 days of naringenin pretreatment, the plasma mean concentration of dasatinib was enhanced compared with without pretreatment. In rats that were pretreated with naringenin, the pharmacokinetics of the orally administered dasatinib (25 mg/kg) was shown to be significantly different from that of dasatinib given without pretreatment (p < 0.05). There was a significant enhancement in pharmacokinetic parameters elimination half-life (T1/2), time to maximum concentration ( Tmax), maximum concentration )Cmax), area under the concentration-time curve (AUC0-t), area under the moment curve (AUMC0-∞), and mean residence time (MRT) by 28.41%, 50%, 103.54%, 72.64%, 115.08%, and 15.19%, respectively (p < 0.05) and suppression in elimination rate constant (Kel), volume of distribution (Vd), and clearance (CL) by 21.09%, 31.13%, and 46.25%, respectively, in comparison with dasatinib alone group (p < 0.05). The enhancement in dasatinib bioavailability and systemic exposure resulted from the significant inhibition of Cyp3a2, Mdr1/P-gp, and Bcrp1 expression and suppression of the dasatinib hepatic and intestinal metabolism, which enhanced the rate of dasatinib absorption and decreased its elimination. CONCLUSION: Concurrent use of naringenin-containing supplements, herbs, or foods with dasatinib may cause serious and potentially life-threatening drug interactions. Further studies are necessary to determine the clinical significance of these findings.

Magnitude of Fruit Juice-Drug Interactions Due to Osmolality-Dependent Fluid Secretion: Differences among Apple, Orange, and Grapefruit Juices.

We recently reported that the gastrointestinal (GI) fluid volume is influenced by the solution osmolality, and proposed that this effect may play a role in beverage-drug interactions. Here, we investigated whether osmolality-dependent fluid secretion can explain the difference in the magnitudes of fruit juice-drug interactions depending on the type of fruit juice (grapefruit juice (GFJ), orange juice (OJ), and apple juice (AJ)). The osmolality of GFJ, OJ, and AJ used in this study was found to be 552, 686, and 749 mOsm/kg, respectively. Measurements of intestinal fluid movement following beverage administration by the in situ closed-loop technique revealed the following rank order for fluid volume in rat ileum: AJ > OJ > GFJ > purified water, suggesting that water movement is dependent on the osmolality of these beverages. Such changes in GI fluid volume are expected to alter the luminal drug concentration, potentially contributing to the magnitude of beverage-drug interactions. Indeed, in vivo pharmacokinetic study in rats revealed that the plasma concentration of atenolol, a low-permeability drug, was the highest after oral administration in purified water, followed by GFJ and OJ, and was the lowest after administration in AJ. In contrast, antipyrine, a high-permeability drug, showed no significant difference in plasma concentration after administration in purified water and fruit juices, suggesting that the absorption of high-permeability drugs is less affected by solution osmolality. Our findings indicate that differences in the magnitude of beverage-drug interactions can be at least partly explained by differences in the osmolality of the beverages ingested.

DrugBank 6.0: the DrugBank Knowledgebase for 2024.

First released in 2006, DrugBank (https://go.drugbank.com) has grown to become the 'gold standard' knowledge resource for drug, drug-target and related pharmaceutical information. DrugBank is widely used across many diverse biomedical research and clinical applications, and averages more than 30 million views/year. Since its last update in 2018, we have been actively enhancing the quantity and quality of the drug data in this knowledgebase. In this latest release (DrugBank 6.0), the number of FDA approved drugs has grown from 2646 to 4563 (a 72% increase), the number of investigational drugs has grown from 3394 to 6231 (a 38% increase), the number of drug-drug interactions increased from 365 984 to 1 413 413 (a 300% increase), and the number of drug-food interactions expanded from 1195 to 2475 (a 200% increase). In addition to this notable expansion in database size, we have added thousands of new, colorful, richly annotated pathways depicting drug mechanisms and drug metabolism. Likewise, existing datasets have been significantly improved and expanded, by adding more information on drug indications, drug-drug interactions, drug-food interactions and many other relevant data types for 11 891 drugs. We have also added experimental and predicted MS/MS spectra, 1D/2D-NMR spectra, CCS (collision cross section), RT (retention time) and RI (retention index) data for 9464 of DrugBank's 11 710 small molecule drugs. These and other improvements should make DrugBank 6.0 even more useful to a much wider research audience ranging from medicinal chemists to metabolomics specialists to pharmacologists.

Relative Oral Bioavailability and Food Effects of Two Sepiapterin Formulations in Healthy Participants.

Sepiapterin is an orally administered drug in development for the treatment of phenylketonuria, an inborn error of metabolism characterized by the deficiency of the phenylalanine-metabolizing enzyme phenylalanine hydroxylase. This study characterized the pharmacokinetics, safety, and tolerability of 2 clinical sepiapterin formulations (Phase 1/2, Phase 3) and the effects of food on the pharmacokinetics of the Phase 3 formulation in healthy participants. In Part A, 18 participants were randomized to one of 2 treatment sequences, each with 4 dosing periods comprising a single dose (20 or 60 mg/kg) of the Phase 1/2 or the Phase 3 formulation with a low-fat diet. In Part B, 14 participants were randomized to one of 2 sequences, each comprising 4 dosing periods of a single dose (20 or 60 mg/kg) of the Phase 3 formulation under fed (high-fat) or fasted conditions. Following oral administration, sepiapterin was quickly absorbed and rapidly and extensively converted to tetrahydrobiopterin (BH4). BH4 was the major circulating active moiety. Under low-fat conditions, the Phase 3 formulation was bioequivalent to the Phase 1/2 formulation at 20 mg/kg, while slightly lower BH4 exposure (approximately 0.81×) for the Phase 3 formulation was observed at 60 mg/kg. BH4 exposure increased to approximately 1.7× under the low-fat condition and approximately 2.8× under the high-fat condition at a dose of either 20 or 60 mg/kg for the Phase 3 formulation, compared with the fasted condition. Both sepiapterin formulations were well tolerated, with no serious or severe adverse events reported. All treatment-emergent adverse events were mild or moderate in severity.

Food Effect on the Pharmacokinetics of VC004, a Tropomyosin Receptor Kinase Inhibitor: A Randomized Crossover Trial in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVE: VC004 is a novel next-generation tropomyosin receptor kinase (TRK) inhibitor that is approved for the treatment of advanced or metastatic NTRK fusion-positive solid tumors and abrogated the drug resistance of the first-generation TRK inhibitors. The objective of the present study was to evaluate the effect of food on the pharmacokinetics and safety of VC004. METHODS: The study was a randomized, open-label, two-period crossover, single-dose, phase I clinical trial. A total of 16 healthy subjects participated the trial. Subjects fasted for 10 h before drug administration in both fasting and fed states. Subjects received VC004 50 mg orally in the fasting state and after a high caloric food in the fed state. Blood samples at the designated time points were collected to determine the plasma concentration of VC004. Safety evaluation in both the fasted and fed periods were assessed via vital sign monitoring and clinical laboratory tests. RESULTS: The maximum plasma concentration (Cmax) of VC004 in fed group decreased by 32.8%, corresponding with the slower absorption rate (time to Cmax (Tmax) delayed by almost 3 h) compared with the fasting group. Ratios of geometric means (GMRs) and 90% confidence intervals (90% CIs) of Cmax, the area under the curve of plasma concentration-time from zero to the last measurable concentration (AUC0-t), and AUC from zero to infinity (AUC0-∞) for VC004 between the two states were 67.18 (58.16-77.60), 103.59 (95.04-112.92) and 103.55 (95.63-112.11), respectively. No serious adverse events (AEs) occurred; only three grade 1 or grade 2 adverse events occurred in the fasted group, who recovered by the end of the study. CONCLUSIONS: The intake of high calorie food decreased the absorption rate and increased the Tmax of VC004, while the AUC values were similar in both groups. No serious adverse event was reported. In conclusion, food does not alter the pharmacokinetics and safety profile of VC004 in a clinically meaningful manner. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT055528120.

Effects of food and ethnicity on the pharmacokinetics of venadaparib, a next-generation PARP inhibitor, in healthy Korean, Caucasian, and Chinese male subjects.

AIM: Venadaparib is a next-generation poly(ADP-ribose) polymerase inhibitor under development for treating gastric cancer. This study aimed to evaluate the effects of food and ethnicity on the pharmacokinetics (PKs) and safety of venadaparib after a single oral administration in healthy Korean, Caucasian, and Chinese male subjects. METHODS: In this randomized, open-label, single-dose, two-sequence, two-period, and crossover study, Korean and Caucasian subjects received venadaparib 80 mg in each period (fasted or fed state) with a seven-day washout. In an open-label, single-dose study, Chinese subjects received venadaparib 80 mg only in the fasted state. Serial blood samples were collected up to 72 h post-dosing. RESULTS: Twelve subjects from each ethnic group completed the study. The geometric mean ratios (90% confidence intervals) of the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the last measurable time point (AUClast) of venadaparib for the fed to fasted state were 0.82 (0.7457-0.9094) and 1.02 (0.9088-1.1339) in Koreans, and 0.77 (0.6871-0.8609) and 0.96 (0.9017-1.0186) in Caucasians, respectively. No statistically significant differences were observed in Cmax (P-value = 0.45) or AUClast (P-value = 0.30) among the three ethnic groups. A single venadaparib dose was well-tolerated. CONCLUSION: The overall systemic exposure of venadaparib was not affected by the high-fat meal, despite delayed absorption with a decreased Cmax in the fed state. The PK profiles were comparable among the Korean, Caucasian, and Chinese subjects. A single venadaparib 80 mg dose was safe and well-tolerated in both fasted and fed states.

The Effects of Jabara Juice on the Intestinal Permeation of Fexofenadine.

Jabara juice and its component narirutin inhibit the activity of organic anion-transporting polypeptides (OATPs) 1A2 and OATP2B1, which are considered to play significant roles in the intestinal absorption of fexofenadine. In this study, we investigated the effects of jabara juice on the intestinal absorption of fexofenadine in mice and the inhibitory effects of jabara juice and narirutin on the permeation of fexofenadine using Caco-2 cell monolayers and LLC-GA5-COL300 cell monolayers. In the in vivo study, the area under the plasma concentration-time curve (AUC) of fexofenadine in mice was increased 1.8-fold by jabara juice. In the permeation study, 5% jabara juice significantly decreased the efflux ratio (ER) of fexofenadine for Caco-2 monolayers. Furthermore, the ERs of fexofenadine and digoxin, which is a typical substrate of P-glycoprotein (P-gp), for LLC-GA5-COL300 cell monolayers were decreased in a concentration-dependent manner by jabara juice extract, suggesting that jabara juice may increase the intestinal absorption of fexofenadine by inhibiting P-gp, rather than by narirutin inhibiting OATPs. The present study showed that jabara juice increases the intestinal absorption of fexofenadine both in vivo and in vitro. The intestinal absorption of fexofenadine may be altered by the co-administration of jabara juice in the clinical setting.

An Update on Drug-Nutrient Interactions and Dental Decay in Older Adults.

In recent decades, the global demographic landscape has undergone a discernible shift that has been characterised by a progressive increase in the proportion of elderly individuals, indicative of an enduring global inclination toward extended lifespans. The aging process, accompanied by physiological changes and dietary patterns, contributes to detrimental deviations in micronutrient consumption. This vulnerable aging population faces heightened risks, including dental caries, due to structural and functional modifications resulting from insufficient nutritional sustenance. Factors such as physiological changes, inadequate nutrition, and the prevalence of multiple chronic pathologies leading to polypharmacy contribute to the challenge of maintaining an optimal nutritional status. This scenario increases the likelihood of drug interactions, both between medications and with nutrients and the microbiome, triggering complications such as dental decay and other pathologies. Since the drug industry is evolving and new types of food, supplements, and nutrients are being designed, there is a need for further research on the mechanisms by which drugs interfere with certain nutrients that affect homeostasis, exemplified by the prevalence of caries in the mouths of older adults. Infectious diseases, among them dental caries, exert serious impacts on the health and overall quality of life of the elderly demographic. This comprehensive review endeavours to elucidate the intricate interplay among drugs, nutrients, the microbiome, and the oral cavity environment, with the overarching objective of mitigating the potential hazards posed to both the general health and dental well-being of older adults. By scrutinising and optimising these multifaceted interactions, this examination aims to proactively minimise the susceptibility of the elderly population to a spectrum of health-related issues and the consequences associated with dental decay.

Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese Adults.

BACKGROUND AND OBJECTIVES: This study was conducted to investigate the effect of high-fat meals on the pharmacokinetics (PK) and safety profile of SAF-189s, a novel ALK/ROS1 inhibitor. METHODS: This was a single-center, phase I, open-label, crossover study in which healthy adults (≥18 years) were randomized (1:1) to two sequences of SAF-189s administration (fasted-fed or fed-fasted) separated by a 14-day washout. After a ≥10-h overnight fast, volunteers received SAF-189s 160 mg orally in a fasted state or 30 min after a high-fat, high-calorie meal. Similarity of pharmacokinetic parameters was concluded if the 90% CI for the geometric mean ratio (GMR) between the fed and fasted group fell within the predefined range of 0.80-1.25. RESULTS: In total, 24 subjects were enrolled and 23 completed the study. SAF-189s maximum plasma concentration (Cmax; GMR: 109.1% [90% CI 103.1-115.4]) was comparable under fed (high-fat meal, n = 24) versus fasted (n = 23) conditions, with no effect on area under the plasma concentration-time curve from time 0 to t (AUC0-t; GMR: 105.1% [90% CI 100.3-110.2]) and AUC from time 0 to infinity (AUC0-∞; GMR: 105.5% [90% CI, 100.6-110.6]). In both groups, the median time to maximum plasma concentration (tmax) was around 6 h and mean plasma half-life (t½) was around 35 h. Fed administration led to a lower incidence of treatment-emergent adverse events (TEAEs; 29.2% vs 54.2%), including gastrointestinal disorders (4.2% vs 41.7%) and headache (0.0% vs 12.5%), versus fasted administration. CONCLUSIONS: A high-fat meal had minimal effect on the pharmacokinetic profile of SAF-189s compared with a fasted state following a single dose of 160 mg. Administration with a high-fat meal led to a lower incidence of TEAEs.

FooDrugs: a comprehensive food-drug interactions database with text documents and transcriptional data.

Food-drug interactions (FDIs) occur when a food item alters the pharmacokinetics or pharmacodynamics of a drug. FDIs can be clinically relevant, as they can hamper or enhance the therapeutic effects of a drug and impact both their efficacy and their safety. However, knowledge of FDIs in clinical practice is limited. This is partially due to the lack of resources focused on FDIs. Here, we describe FooDrugs, a database that centralizes FDI knowledge retrieved from two different approaches: a natural processing language pipeline that extracts potential FDIs from scientific documents and clinical trials and a molecular similarity approach based on the comparison of gene expression alterations caused by foods and drugs. FooDrugs database stores a total of 3 430 062 potential FDIs, with 1 108 429 retrieved from scientific documents and 2 321 633 inferred from molecular data. This resource aims to provide researchers and clinicians with a centralized repository for potential FDI information that is free and easy to use. Database URL:  https://zenodo.org/records/8192515 Database DOI:  https://doi.org/10.5281/zenodo.6638469.