Catherine Guittet1, Maria Manso1, Ingrid Burton2, Luc-André Granier1, Frédéric Marçon3. 1. Advicenne Pharma, Nîmes, France. 2. ClinBay, Baisy-Thy, Belgium. 3. Groupe de recherche en pharmacotechnie pédiatrique, Pharmacie à Usage Intérieur, Centre Hospitalier Universitaire d'Amiens, Amiens, France. marcon.frederic@chu-amiens.fr.
Abstract
PURPOSE: The objective of this study was to assess the bioavailability and the sedative effect of a single-dose administration of an innovative oral solution of midazolam containing γ-cyclodextrins (ADV6209). METHODS: A bioavailability study with a standard two-sequences, two-periods, and crossover design was conducted. Subjects randomly received 15 mg of ADV6209 by oral route followed by 5 mg of the reference drug (midazolam hydrochloride intravenous solution (Hypnovel®, Roche) by intravenous route or vice versa. Blood samples were drawn at different time points to measure midazolam and its metabolite α-hydroxymidazolam concentrations. Non-compartmental pharmacokinetic methods were used to calculate main pharmacokinetic parameters and absolute bioavailability. RESULTS:Caucasian healthy subjects (n = 12) were included in the study. ADV6209 had a bioavailability of 39.6%. The oral elimination half-life with ADV6209 was slightly shorter than with the reference i.v. form (2.66 h versus 2.99 h). The sedative effect was observed 27.5 ± 15.5 min after oral administration for a duration of 48.5 ± 35.4 min. Double peak phenomenon was observed in 5 patients. CONCLUSIONS: Cyclodextrins have little impact on midazolam oral bioavailability and the pharmacokinetics parameters of midazolam formulation ADV6209 are close to those reported previously.
RCT Entities:
PURPOSE: The objective of this study was to assess the bioavailability and the sedative effect of a single-dose administration of an innovative oral solution of midazolam containing γ-cyclodextrins (ADV6209). METHODS: A bioavailability study with a standard two-sequences, two-periods, and crossover design was conducted. Subjects randomly received 15 mg of ADV6209 by oral route followed by 5 mg of the reference drug (midazolam hydrochloride intravenous solution (Hypnovel®, Roche) by intravenous route or vice versa. Blood samples were drawn at different time points to measure midazolam and its metabolite α-hydroxymidazolam concentrations. Non-compartmental pharmacokinetic methods were used to calculate main pharmacokinetic parameters and absolute bioavailability. RESULTS: Caucasian healthy subjects (n = 12) were included in the study. ADV6209 had a bioavailability of 39.6%. The oral elimination half-life with ADV6209 was slightly shorter than with the reference i.v. form (2.66 h versus 2.99 h). The sedative effect was observed 27.5 ± 15.5 min after oral administration for a duration of 48.5 ± 35.4 min. Double peak phenomenon was observed in 5 patients. CONCLUSIONS:Cyclodextrins have little impact on midazolam oral bioavailability and the pharmacokinetics parameters of midazolam formulation ADV6209 are close to those reported previously.
Authors: Margreke J E Brill; Anne van Rongen; Aletta P I Houwink; Jacobus Burggraaf; Bert van Ramshorst; René J Wiezer; Eric P A van Dongen; Catherijne A J Knibbe Journal: Clin Pharmacokinet Date: 2014-10 Impact factor: 6.447
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Authors: Jang-Ik Lee; Diego Chaves-Gnecco; Janet A Amico; Patricia D Kroboth; John W Wilson; Reginald F Frye Journal: Clin Pharmacol Ther Date: 2002-12 Impact factor: 6.875