Abstract
BackgroundMitiglinide is a widely used agent for diabetic treatment. We established a pharmacokinetic-pharmacodynamic (PK-PD) model to illustrate the relationship between mitiglinide plasma concentration and its glucose lowering effects in healthy volunteers.MethodsThe volunteers participated in the test after the administration of a single dose of 10 mg mitiglinide. The drug concentration in Plasma and the values of glucose levels were determined by LC-MS/MS assay and hexokinase method. A PK-PD model was established with a series of equations to describe the relationship between plasma medicine and glucose, and the equations were solved numerically and fitted to the data with the Phoenix NLME software.ResultsThe results of the two-compartment model analysis were based on the maximum likelihood criterion and visual inspection of the fittings. The terminal elimination half-life (t1/2) was 1.69 ± 0.16 h and the CL/F was 7.80 ± 1.84 L/h. The plasma glucose levels began to decline by 0.2 h, and hit its bottom decreasing values of 2.6 mg/L at 0.5 h after administration. The calculated parameter and fitting curve indicated that the model established in our experiment fitted well.ConclusionsA PK/PD model illustrates that the relationship between mitiglinide concentration in plasma and glucose lowering effect in healthy volunteers was established. The results of our experiment suggested that the model can be used reasonably to predict the relationship between PK and PD in mitiglinide, which could be used in diabetes mellitus dosage control in clinical trials and other fields.
Highlights
Mitiglinide is a widely used agent for diabetic treatment
PK parameters were obtained by simultaneously fitting the plasma concentration data after oral administration of mitiglinide (10 mg) to volunteers using the 2-compartment PK model (Table 1)
PK parameters were obtained by simultaneously fitting the plasma concentration data after oral administration of mitiglinide to volunteers using the 2-compartment model
Summary
Mitiglinide is a widely used agent for diabetic treatment. We established a pharmacokineticpharmacodynamic (PK-PD) model to illustrate the relationship between mitiglinide plasma concentration and its glucose lowering effects in healthy volunteers. ATPsensitive K+ (KATP) channels exists widely in pancreatic cells, cardiac, smooth and skeletal muscles, and central nervous system [4]. Different KATP-channel may exist in different tissues, Kir6.2/SUR1 for β-cells, some neurons cardiac, Kir6.2/SUR2A for skeletal. Mitiglinide is a rapid acting drug for diabetic drugs, which is selectively active on KATP channel of Kir6.2/ SUR1 [6, 7]. The PK property of 24 volunteers who received oral administration mitiglinide at a single dose from 5 to 20 mg/kg was studied [10]. The maximum plasma concentration (Cmax) in volunteers with mitiglinide from 5 to 20 mg/kg was 565.30
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
