Ustekinumab pharmacokinetics after subcutaneous administration in swine model. 2021

Tomasz Grabowski, and Artur Burmańczuk, and Rafał Derlacz, and Tadeusz Stefaniak, and Anna Rząsa, and Jacek Borkowski
Polpharma Biologics SA, 80-172 Gdańsk, Poland.

BACKGROUND Due to multiple similarities in the structure and physiology of human and pig skin, the pig model is extremely useful for biological drug testing after subcutaneous administration. Knowledge of the differences between subcutaneous injection sites could have a significant impact on the absorption phase and pharmacokinetic profiles of biological drugs. OBJECTIVE This study aimed to analyze the impact of administration site on pharmacokinetics and selected biochemical and hematological parameters after a single subcutaneous administration of ustekinumab in pigs. Drug concentrations in blood plasma were analyzed by enzyme-linked immunosorbent assay. Pharmacokinetic analyses were performed based on raw data using Phoenix WinNonlin 8.1 software and ThothPro v 4.1. METHODS The study included 12 healthy, female, large white piglets. Each group received a single dose of ustekinumab given as a 1 mg/kg subcutaneous injection into the internal part of the inguinal fold or the external part of the inguinal fold. RESULTS The differences in absorption rate between the internal and external parts of the inguinal fold were not significant. However, the time of maximal concentration, clearance, area under the curve calculated between zero and mean residence time and mean residence time between groups were substantially different (p > 0.05). The relative bioavailability after administration of ustekinumab into the external part of the inguinal fold was 40.36% lower than after administration of ustekinumab into the internal part of the inguinal fold. CONCLUSIONS Healthy breeding pigs are a relevant model to study the pharmacokinetic profile of subcutaneously administered ustekinumab.

UI MeSH Term Description Entries
D007279 Injections, Subcutaneous Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin. Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D003879 Dermatologic Agents Drugs used to treat or prevent skin disorders or for the routine care of skin. Agent, Dermatologic,Agent, Dermatological,Agents, Dermatologic,Dermatologic Agent,Dermatological Agents,Agents, Dermatological,Dermatological Agent
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000069549 Ustekinumab A humanized monoclonal antibody that binds to IL-12 and IL-23 and is used as a DERMATOLOGIC AGENT in the treatment of patients with plaque PSORIASIS who have not responded to other therapies. CNTO 1275,CNTO-1275,Stelara
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001682 Biological Availability The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action. Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D023421 Models, Animal Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing. Experimental Animal Models,Laboratory Animal Models,Animal Model,Animal Model, Experimental,Animal Model, Laboratory,Animal Models,Animal Models, Experimental,Animal Models, Laboratory,Experimental Animal Model,Laboratory Animal Model,Model, Animal,Model, Experimental Animal,Model, Laboratory Animal,Models, Experimental Animal,Models, Laboratory Animal
D034421 Sus scrofa A species of SWINE, in the family Suidae, comprising a number of subspecies including the domestic pig Sus scrofa domestica. Pig, Domestic,Sus scrofa domesticus,Wild Boar,Sus scrofa domestica,Boar, Wild,Boars, Wild,Domestic Pig,Domestic Pigs,Pigs, Domestic,Wild Boars

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