Population pharmacokinetic analysis of apomorphine sublingual film or subcutaneous apomorphine in healthy subjects and patients with Parkinson's disease.
Autor: | Agbo F; Sunovion Pharmaceuticals Inc, Fort Lee, New Jersey, USA., Crass RL; Ann Arbor Pharmacometrics Group, Inc, Ann Arbor, Michigan, USA., Chiu YY; Sunovion Pharmaceuticals Inc, Fort Lee, New Jersey, USA., Chapel S; Ann Arbor Pharmacometrics Group, Inc, Ann Arbor, Michigan, USA., Galluppi G; Sunovion Pharmaceuticals Inc, Marlborough, Massachusetts, USA., Blum D; Sunovion Pharmaceuticals Inc, Marlborough, Massachusetts, USA., Navia B; Sunovion Pharmaceuticals Inc, Marlborough, Massachusetts, USA. |
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Jazyk: | angličtina |
Zdroj: | Clinical and translational science [Clin Transl Sci] 2021 Jul; Vol. 14 (4), pp. 1464-1475. Date of Electronic Publication: 2021 May 02. |
DOI: | 10.1111/cts.13008 |
Abstrakt: | Apomorphine is an on-demand treatment of "OFF" episodes in patients with Parkinson's disease (PD). A joint parent-metabolite population pharmacokinetic (PK) model characterized apomorphine and apomorphine-sulfate following administration of apomorphine sublingual film (APL) and two formulations of subcutaneous apomorphine. Overall, 2485 samples from 87 healthy subjects and 71 patients with PD and "OFF" episodes were analyzed using nonlinear mixed-effects modeling. Apomorphine PK was adequately described by a two-compartment model with first-order transit absorption via both routes of administration and first-order metabolism to apomorphine-sulfate with one-compartment disposition and first-order elimination. Bioavailability of apomorphine sublingual film was ~ 18% relative to subcutaneous apomorphine. Among covariates tested, only body weight had a large effect on apomorphine exposure (maximum plasma concentration and area under the concentration-time curve [AUC (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.) |
Databáze: | MEDLINE |
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