In vivo drug dissolution in the gastrointestinal (GI) tract is largely unmeasured. The purpose of this clinical study is to evaluate the in vivo drug dissolution and systemic absorption of modified release formulations of the BCS Class II drug Glipizide by direct sampling of stomach and small intestinal luminal content, blood, urine and feces. Expanding current knowledge of drug dissolution in vivo will help to establish physiologically relevant in vitro models predictive of drug dissolution.
This is an in vivo study designed to acquire human gastrointestinal (GI) physiology data from healthy subjects which are necessary for mechanistic absorption model development. Each subject will be asked to complete a single dosing phase. The dosing phase will include collection of fluids from stomach and gastrointestinal (GI) tract through intubation (putting a GI tube from mouth into stomach and intestines), blood, urine and feces, and measure glipizide concentrations. The objectives of this study are, as follows: Objective #1: To characterize the plasma, gastrointestinal fluid, urine, and feces concentrations of glipizide after oral administration of modified release formulations; Objective #2: To compare the pharmacokinetics of glipizide between the two modified release formulations; Objective #3: To collect gastrointestinal physiology data in volunteers receiving an oral MR formulation of glipizide. These in vivo results will be used to validate in vitro dissolution methods and to support computational and mathematical modeling efforts, in order to develop an oral drug product optimization process that may be applied to future drugs to maximize oral drug safety and efficacy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
40
Participants are randomized to take one tablet of this study drug by mouth.
Participants are randomized to take one tablet of this study drug by mouth.
Participants will take one tablet of this study drug by mouth.
Participants will take 1 mg of this study drug dissolved in 40 ml glucose solution by mouth.
University of Michigan
Ann Arbor, Michigan, United States
RECRUITINGAverage Area Under the Plasma Concentration-time Curve to infinite time (AUCinfinity) of Glipizide After a Single Dose of Glipizide with Gastrointestinal Intubation and between Two Modified Release Glipizide formulations
Average Area Under the Plasma Concentration-time Curve to infinite time (AUCinfinity) of Glipizide will be measured at multiple timepoints over a 78 hour period at each of the two study phases
Time frame: From time 0 to 78 hours
Plasma Cmax of Glipizide After a Single Dose of Glipizide with Gastrointestinal Intubation and between Two Modified Release Glipizide formulations
Peak Plasma Concentration of Glipizide (Cmax) will be measured at multiple timepoints over a 78 hour period at the study phase
Time frame: From time 0 to 78 hours
Plasma Tmax of Glipizide After a Single Dose of Glipizide with Gastrointestinal Intubation and between Two Modified Release Glipizide formulations
The time it takes to reach the maximum concentration of Glipizide in Plasma (Tmax) will be measured at multiple timepoints over a 78 hour period at the study phase
Time frame: From time 0 to 78 hours
Urine and Feces concentrations of Glipizide After a Single Dose of Glipizide with Gastrointestinal Intubation and between Two Modified Release Glipizide formulations
Recovery of Glipizide in urine and feces will be measured at multiple timepoints over a 78 hour period at the study phase
Time frame: From time 0 to 78 hours
Maximum Gastrointestinal fluid concentration of Glipizide after Oral Administration of a Single Dose Modified Released Formulation of Glipizide
The concentration of Glipizide in gastrointestinal fluid (stomach, duodenum, jejunum and ileum) will be measured at multiple timepoints over a 7 hour period using a 4-port G.I Intubation Catheter
Time frame: From time 0 to 7 hours
Gastrointestinal pH after Oral Administration of Modified Release Formulation of Glipizide
Gastrointestinal pH will be measured ex-vivo in gastrointestinal fluid samples collected through gastrointestinal intubation catheter over a duration of 7 hours.
Time frame: From time 0 to 7 hours
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