AIMS: The purpose of the present study was to assess the pharmacokinetics of the novel selective 5-HT4 receptor agonist SDZ HTF 919 (HTF) including food effect, absolute bioavailability, interoccasion and intersubject variabilities. METHODS: In the randomized, open-label, three treatment, four period crossover study, HTF was administered to 12 young healthy male subjects as a 12 mg tablet (twice under fasted and once under fed conditions) and a 3 mg intravenous (i.v.) infusion over 40 min (fasted). Pharmacokinetic parameters were obtained by noncompartmental methods. A more comprehensive pharmacokinetic characterization was achieved by integrated modelling of oral (p.o.) and i.v. data. To describe the absorption phase a Weibull function and a classical first order input function were compared. RESULTS: Noncompartmental pharmacokinetic analysis revealed a rapid absorption (tmax 1.3 h, fasted), an absolute bioavailability of 11+/-3%, a biphasic disposition phase with a terminal half-life of 11+/-5 h, a clearance of 77+/-15 l h-1, and a volume of distribution at steady state of 368+/-223 l. The coefficients of interoccasion and interindividual variability in Cmax and AUC ranged between 17 and 28%. Food intake caused a delay (tmax 2.0 h) and decrease in absorption with consequently lower systemic exposure ( approximately 5% absolute bioavailability). Integrated p.o./i.v. pharmacokinetic modelling with a Weibull input function allowed accurate description of individual profiles. Modelling of the data from the p.o. dosing improved the description of the terminal phase by inclusion of the i. v. data and additionally provided quantitative characterization of the absorption phase. CONCLUSIONS: The pharmacokinetics of HTF could be well described by an integrated modelling approach for both p.o. and i.v. data. The derived model will provide guidance in the design of future studies.
RCT Entities:
AIMS: The purpose of the present study was to assess the pharmacokinetics of the novel selective 5-HT4 receptor agonist SDZHTF 919 (HTF) including food effect, absolute bioavailability, interoccasion and intersubject variabilities. METHODS: In the randomized, open-label, three treatment, four period crossover study, HTF was administered to 12 young healthy male subjects as a 12 mg tablet (twice under fasted and once under fed conditions) and a 3 mg intravenous (i.v.) infusion over 40 min (fasted). Pharmacokinetic parameters were obtained by noncompartmental methods. A more comprehensive pharmacokinetic characterization was achieved by integrated modelling of oral (p.o.) and i.v. data. To describe the absorption phase a Weibull function and a classical first order input function were compared. RESULTS: Noncompartmental pharmacokinetic analysis revealed a rapid absorption (tmax 1.3 h, fasted), an absolute bioavailability of 11+/-3%, a biphasic disposition phase with a terminal half-life of 11+/-5 h, a clearance of 77+/-15 l h-1, and a volume of distribution at steady state of 368+/-223 l. The coefficients of interoccasion and interindividual variability in Cmax and AUC ranged between 17 and 28%. Food intake caused a delay (tmax 2.0 h) and decrease in absorption with consequently lower systemic exposure ( approximately 5% absolute bioavailability). Integrated p.o./i.v. pharmacokinetic modelling with a Weibull input function allowed accurate description of individual profiles. Modelling of the data from the p.o. dosing improved the description of the terminal phase by inclusion of the i. v. data and additionally provided quantitative characterization of the absorption phase. CONCLUSIONS: The pharmacokinetics of HTF could be well described by an integrated modelling approach for both p.o. and i.v. data. The derived model will provide guidance in the design of future studies.
Authors: R Meir; C Beglinger; J P Dederding; B Meyer-Wyss; M Fumagalli; A Rowedder; J Turberg; R Brignoli Journal: Schweiz Med Wochenschr Date: 1992-06-13
Authors: Shuang-Qing Zhang; Ziyaur Rahman; Sridhar Thumma; Michael A Repka; Guo-Hua Chen; San-Ming Li Journal: Drug Dev Ind Pharm Date: 2009-01 Impact factor: 3.225
Authors: J Tack; M Camilleri; L Chang; W D Chey; J J Galligan; B E Lacy; S Müller-Lissner; E M M Quigley; J Schuurkes; J H De Maeyer; V Stanghellini Journal: Aliment Pharmacol Ther Date: 2012-02-22 Impact factor: 8.171
Authors: Valentina Noemi Madia; Antonella Messore; Francesco Saccoliti; Valeria Tudino; Alessandro De Leo; Daniela De Vita; Martina Bortolami; Luigi Scipione; Ivano Pindinello; Roberta Costi; Roberto Di Santo Journal: Antiinflamm Antiallergy Agents Med Chem Date: 2020