Pharmacokinetics and Comparative Bioavailability of Apomorphine Sublingual Film and Subcutaneous Apomorphine Formulations in Patients with Parkinson’s Disease and “OFF” Episodes: Results of a Randomized, Three-Way Crossover, Open-Label Study
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Le résumé fourni par la source
In a pivotal study, apomorphine sublingual film (APL; KYNMOBI ® ) was an effective and generally well-tolerated on-demand treatment of “OFF” episodes in patients with Parkinson’s disease (PD), approved across the dose range of 10–30 mg. Pharmacokinetics and comparative bioavailability of APL and two subcutaneous (SC) apomorphine formulations (SC-APO [APOKYN ® ] and SC-APO-GO [APO-go ® PEN]) were evaluated in a randomized, three-way crossover, open-label study (NCT03292016). Patients with PD and “OFF” episodes received an open-label randomized sequence of single doses of SC-APO and SC-APO-GO at the currently prescribed dose (2/3/4/5 mg) and APL doses with similar plasma exposure (15/20/25/30 mg) with ≥ 1-day washout between formulations. Plasma pharmacokinetics of apomorphine and apomorphine sulfate (major inactive metabolite) were measured 0–6 h postdose. Median time to maximum plasma concentration ( t max ) of apomorphine was 0.63–0.75 h for APL and 0.25–0.38 h for SC-APO and SC-APO-GO. Geometric mean maximum plasma concentration ( C max ) of apomorphine was 4.31–11.2 ng/ml across APL doses and was generally lower compared with SC apomorphine formulations within dose groups. Area under the concentration-time curve from time 0 to infinity (AUC ∞ ) was similar across apomorphine formulations within most dose groups. Relative bioavailability of APL was ~ 17% of SC apomorphine by AUC ∞ ; SC-APO and SC-APO-GO had similar bioavailability (98% and 83% by AUC ∞ and C max , respectively). Apomorphine sulfate exposure was ~ three-fold higher for APL versus SC-APO and SC-APO-GO by AUC ∞ and C max . In patients with PD and “OFF” episodes, APL demonstrated lower C max and relative bioavailability but similar exposures (AUCs) versus SC apomorphine within the approved dose range. ClinicalTrials.gov, NCT03292016.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Pharmacokinetics and Comparative Bioavailability of Apomorphine Sublingual Film and Subcutaneous Apomorphine Formulations in Patients with Parkinson’s Disease and “OFF” Episodes: Results of a Randomized, Three-Way Crossover, Open-Label Study
- Date Crossref
- 15/05/2021
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Sunovion (United States) pays non établi dans la noticeEntreprise
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Vion Pharmaceuticals (United States) pays non établi dans la noticeEntreprise
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Parkinson's Research and Education Foundation pays non établi dans la noticeOrganisation à but non lucratif
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Inc. Merck & Co. pays non établi dans la noticeEntreprise
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Clinical Pharmacology pays non établi dans la noticeÉtablissement de santé
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Parkinson's Disease and Movement Disorders Center of Boca Raton pays non établi dans la noticeInstitution
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Parkinson's Disease Treatment Center of Southwest Florida pays non établi dans la noticeInstitution
Sunovion (United States), Vion Pharmaceuticals (United States) et Parkinson's Research and Education Foundation, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.