Biopharmaceutics & drug disposition · 2013
Therapeutic drug monitoring and pharmacokinetic compartmental analysis of sulpiride double-peak absorption profile after oral administration to human volunteers.
Клиническое исследование I фазыСтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Helmy Sally A
Аннотация
BACKGROUND: The pharmacokinetics of oral drugs that exhibit double peaks cannot be described adequately by using conventional compartmental models.
OBJECTIVE: The aim of this study was to describe the double-peak plasma pharmacokinetic profile of sulpiride after oral administration to healthy volunteers based on physiological and biopharmaceutical considerations.
METHODS: A single 100 mg dose of sulpiride was given to 16 healthy volunteers. Blood samples were drawn at different times and analysed by a validated HPLC assay method. Plasma profiles were evaluated by non-compartmental and compartmental approaches.
RESULTS: The non-compartmental parameters determined were k (0.079±0.008 h(-1)), t1/2 (9.0±2.9 h), Vd /F (330.5±87.3 L), Cl/F (38.2±9.8 L/h) and AUC0→∞ (1402.5±404.7 ng.h/mL). The compartmental analysis was described appropriately using a two-compartment body model, with first order absorption from two different sites in the gut. The parameters determined were k21 (0.68±0.2 h(-1)), ka1 (0.7±0.27 h(-1)), ka2 (2.7±1.8 h(-1)) Vc/F (45.1±15.7 L), α (33.3±1.5 h(-1)), β (0.11±0.03 h(-1)) and time for the beginning of the absorption from the second site (4.4±2.1 h).
CONCLUSION: The developed analytical method was suitable for use in pharmacokinetic studies and therapeutic drug monitoring implementation. Sulpiride was well tolerated by the patients without any serious adverse events being observed. The double peaks in the serum concentration-time profiles could be due to differential rates of absorption along the gastrointestinal tract. The discontinuous absorption model with two sites of absorption was adequate to describe the double-peak of the sulpiride plasma profile. ClinicalTrials. gov identifiers: NCT01777685.
OBJECTIVE: The aim of this study was to describe the double-peak plasma pharmacokinetic profile of sulpiride after oral administration to healthy volunteers based on physiological and biopharmaceutical considerations.
METHODS: A single 100 mg dose of sulpiride was given to 16 healthy volunteers. Blood samples were drawn at different times and analysed by a validated HPLC assay method. Plasma profiles were evaluated by non-compartmental and compartmental approaches.
RESULTS: The non-compartmental parameters determined were k (0.079±0.008 h(-1)), t1/2 (9.0±2.9 h), Vd /F (330.5±87.3 L), Cl/F (38.2±9.8 L/h) and AUC0→∞ (1402.5±404.7 ng.h/mL). The compartmental analysis was described appropriately using a two-compartment body model, with first order absorption from two different sites in the gut. The parameters determined were k21 (0.68±0.2 h(-1)), ka1 (0.7±0.27 h(-1)), ka2 (2.7±1.8 h(-1)) Vc/F (45.1±15.7 L), α (33.3±1.5 h(-1)), β (0.11±0.03 h(-1)) and time for the beginning of the absorption from the second site (4.4±2.1 h).
CONCLUSION: The developed analytical method was suitable for use in pharmacokinetic studies and therapeutic drug monitoring implementation. Sulpiride was well tolerated by the patients without any serious adverse events being observed. The double peaks in the serum concentration-time profiles could be due to differential rates of absorption along the gastrointestinal tract. The discontinuous absorption model with two sites of absorption was adequate to describe the double-peak of the sulpiride plasma profile. ClinicalTrials. gov identifiers: NCT01777685.