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Effect of Food on the Pharmacokinetics of Tenofovir Amibufenamide: A Phase I, Randomized, Open-Label, Two-Period Crossover Trial in Healthy Adult Subjects. 2023

Jian Liu, and Minglan Wu, and Jiejing Kai, and Meihua Lin, and Yunliang Zheng, and Yiya Jiang, and Qian Huang, and You Zhai, and Yunqing Qiu
Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People's Republic of China.

Tenofovir amibufenamide (TMF) is a novel nucleotide reverse transcriptase inhibitor. The aim of this study was to investigate the effect of food on the single-dose pharmacokinetic properties of TMF. In this open-label, randomized, crossover study, after an overnight fast, eligible subjects received a single 25 mg dose of TMF tablet, either under fasted conditions or following consumption of a high-fat, high-calorie meal, followed by a two-week washout period. Blood samples were collected until 144 h after administration. TMF and its metabolite, tenofovir (TFV), were analyzed using validated liquid chromatography-tandem mass spectrometry methods. The geometric mean ratio (GMR) and the corresponding 90% confidence interval (CI) values of AUC0-t, AUC0-∞, and Cmax were acquired for analysis. The absence of an effect of food was indicated if the 90% CI values were within the predefined equivalence limits of 80%-125%. Safety and tolerability were also assessed. For TMF, adjusted GMR (90% CI) values for the fed versus fasted states were 150.28% (125.36%-180.16%), 158.24% (130.42%-192.00%), and 57.65% (45.68%-72.76%) for AUC0-t, AUC0-∞, and Cmax, respectively. For TFV, the GMR (90% CI) of Cmax was 82.00% (74.30%-90.49%) after administration under fed conditions, slightly outside the bioequivalence boundary of 80%-125%, while the corresponding values for AUC0-t and AUC0-∞ were within range. The absorption of TMF was delayed by food, with median Tmax values of 0.33 and 1.00 h in fasted and fed conditions, respectively. The adverse events observed in subjects were all mild. Our results demonstrated that TMF tablets were well-tolerated in healthy volunteers. When TMF tablets were taken with food, Tmax was delayed and exposures of TMF and TFV were higher than under fasted conditions. The modest changes observed are not considered clinically relevant, so TMF can be taken with or without food.

UI MeSH Term Description Entries
D005215 Fasting Abstaining from FOOD. Hunger Strike,Hunger Strikes,Strike, Hunger,Strikes, Hunger
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000068698 Tenofovir An adenine analog REVERSE TRANSCRIPTASE INHIBITOR with antiviral activity against HIV-1 and HEPATITIS B. It is used to treat HIV INFECTIONS and CHRONIC HEPATITIS B, in combination with other ANTIVIRAL AGENTS, due to the emergence of ANTIVIRAL DRUG RESISTANCE when it is used alone. (R)-9-(2-phosphonylmethoxypropyl)adenine,9-(2-Phosphonomethoxypropyl)adenine,9-(2-Phosphonylmethoxypropyl)adenine,9-(2-Phosphonylmethoxypropyl)adenine, (+-)-isomer,9-(2-Phosphonylmethoxypropyl)adenine, (R)-isomer - T357098,9-(2-Phosphonylmethoxypropyl)adenine, (S)-isomer,9-PMPA (tenofovir),Tenofovir Disoproxil,Tenofovir Disoproxil Fumarate,Viread,Disoproxil Fumarate, Tenofovir,Disoproxil, Tenofovir,Fumarate, Tenofovir Disoproxil
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D013607 Tablets Solid dosage forms, of varying weight, size, and shape, which may be molded or compressed, and which contain a medicinal substance in pure or diluted form. (Dorland, 28th ed) Tablet
D013810 Therapeutic Equivalency The relative equivalency in the efficacy of different modes of treatment of a disease, most often used to compare the efficacy of different pharmaceuticals to treat a given disease. Bioequivalence,Clinical Equivalency,Equivalency, Therapeutic,Generic Equivalency,Clinical Equivalencies,Equivalencies, Clinical,Equivalencies, Therapeutic,Equivalency, Clinical,Therapeutic Equivalencies,Bioequivalences,Equivalencies, Generic,Equivalency, Generic,Generic Equivalencies
D018592 Cross-Over Studies Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed) Cross-Over Design,Cross-Over Trials,Crossover Design,Crossover Studies,Crossover Trials,Cross Over Design,Cross Over Studies,Cross Over Trials,Cross-Over Designs,Cross-Over Study,Crossover Designs,Crossover Study,Design, Cross-Over,Design, Crossover,Designs, Cross-Over,Designs, Crossover,Studies, Cross-Over,Studies, Crossover,Study, Cross-Over,Study, Crossover,Trial, Cross-Over,Trial, Crossover,Trials, Cross-Over,Trials, Crossover
D018894 Reverse Transcriptase Inhibitors Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. Reverse Transcriptase Inhibitor,Inhibitors, Reverse Transcriptase,Inhibitor, Reverse Transcriptase,Transcriptase Inhibitor, Reverse
D019540 Area Under Curve A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992) AUC,Area Under Curves,Curve, Area Under,Curves, Area Under,Under Curve, Area,Under Curves, Area
D064368 Healthy Volunteers Persons with no known significant health problems who are recruited to participate in research to test a new drug, device, or intervention as controls for a patient group. (from http://clinicalcenter.nih.gov/recruit/volunteers.html, accessed 2/14/2013) Healthy Participants,Healthy Subjects,Human Volunteers,Normal Volunteers,Healthy Participant,Healthy Subject,Healthy Volunteer,Human Volunteer,Normal Volunteer,Participant, Healthy,Participants, Healthy,Subject, Healthy,Subjects, Healthy,Volunteer, Healthy,Volunteer, Human,Volunteer, Normal,Volunteers, Human,Volunteers, Normal

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