356-P: Population Pharmacokinetic Modeling of Dasiglucagon in Subjects with Type 1 Diabetes Mellitus
| Autor: | Stine Just Maarbjerg, Paul M. Diderichsen, Han Witjes, Anders H. Valeur, Carsten Boye Knudsen, Ramin Tehranchi |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Diabetes. 70 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db21-356-p |
| Popis: | To quantify the impact of subject covariates on pharmacokinetics (PK) of the novel, ready-to-use glucagon analog dasiglucagon, we developed a population PK model. Dasiglucagon pharmacokinetics was dose linear in the tested dose range (0.1 to 1.0 mg) and described by a 1-compartment model with first-order absorption and elimination, including an absorption lag time and standard allometric scaling by body weight. The final model included injection site, age as covariates on bioavailability, and MDRD eGFR and sex as covariates on apparent clearance and absorption rate constant, respectively. The model also accounted for reduced drug content at end of shelf-life storage. Based on visual predictive checks the model reliably predicted observed data. The effect of covariates on dasiglucagon exposure measured by area under the concentration time curve (AUC) are shown in the figure below (predicted [95% CI]). AUCs are relative to the AUC predicted for a typical subject aged ≥ 24 years, weighing 78 kg with normal kidney function (eGFR 95 mL/min/1.73m2) and receiving a 0.6 mg dose of dasiglucagon in the abdomen. The model-predicted effects of PK covariates on dasiglucagon AUC generally fell within the observed AUC from the analysis population receiving 0.6 mg dasiglucagon (red markers, median, and 5th-95th percentile interval, n = 321) and observed across the trials to result in reliable recovery from hypoglycemia. Disclosure C. B. Knudsen: Employee; Self; Zealand Pharma A/S, Employee; Spouse/Partner; Novo Nordisk A/S, Stock/Shareholder; Self; Zealand Pharma A/S, Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. A. H. Valeur: Employee; Self; Zealand Pharma A/S. S. Maarbjerg: Employee; Self; Zealand Pharma A/S, Employee; Spouse/Partner; Zealand Pharma A/S, Stock/Shareholder; Self; Novo Nordisk A/S, Stock/Shareholder; Spouse/Partner; Zealand Pharma A/S. R. Tehranchi: Employee; Self; Zealand Pharma A/S. P. Diderichsen: Consultant; Self; Boehringer Ingelheim International GmbH, Zealand Pharma A/S, Employee; Self; Certara Netherlands bv. H. Witjes: Employee; Self; Certara. |
| Databáze: | OpenAIRE |
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