| Title |
Population pharmacokinetic modeling of glibenclamide in poorly controlled South African type 2 diabetic subjects
|
|---|---|
| Published in |
Clinical Pharmacology : Advances and Applications, July 2016
|
| DOI | 10.2147/cpaa.s102676 |
| Pubmed ID | |
| Authors |
Virendra Rambiritch, Poobalan Naidoo, Breminand Maharaj, Goonaseelan Pillai |
| Abstract |
The aim of this study was to describe the pharmacokinetics (PK) of glibenclamide in poorly controlled South African type 2 diabetic subjects using noncompartmental and model-based methods. A total of 24 subjects with type 2 diabetes were administered increasing doses (0 mg/d, 2.5 mg/d, 5 mg/d, 10 mg/d, and 20 mg/d) of glibenclamide daily at 2-week intervals. Plasma glibenclamide, glucose, and insulin determinations were performed. Blood sampling times were 0 minute, 30 minutes, 60 minutes, 90 minutes, and 120 minutes (post breakfast sampling) and 240 minutes, 270 minutes, 300 minutes, 330 minutes, 360 minutes, and 420 minutes (post lunch sampling) on days 14, 28, 42, 56, and 70 for doses of 0 mg, 2.5 mg, 5.0 mg, 10 mg, and 20 mg, respectively. Blood sampling was performed after the steady state was reached. A total of 24 individuals in the data set contributed to a total of 841 observation records. The PK was analyzed using noncompartmental analysis methods, which were implemented in WinNonLin(®), and population PK analysis using NONMEM(®). Glibenclamide concentration data were log transformed prior to fitting. A two-compartmental disposition model was selected after evaluating one-, two-, and three-compartmental models to describe the time course of glibenclamide plasma concentration data. The one-compartment model adequately described the data; however, the two-compartment model provided a better fit. The three-compartment model failed to achieve successful convergence. A more complex model, to account for enterohepatic recirculation that was observed in the data, was unsuccessful. In South African diabetic subjects, glibenclamide demonstrates linear PK and was best described by a two-compartmental model. Except for the absorption rate constant, the other PK parameters reported in this study are comparable to those reported in the scientific literature. The study is limited by the small study sample size and inclusion of poorly controlled type 2 diabetic subjects. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 15 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Lecturer | 3 | 20% |
| Student > Ph. D. Student | 3 | 20% |
| Researcher | 2 | 13% |
| Student > Master | 2 | 13% |
| Student > Bachelor | 1 | 7% |
| Other | 1 | 7% |
| Unknown | 3 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 6 | 40% |
| Medicine and Dentistry | 3 | 20% |
| Mathematics | 2 | 13% |
| Agricultural and Biological Sciences | 1 | 7% |
| Biochemistry, Genetics and Molecular Biology | 1 | 7% |
| Other | 0 | 0% |
| Unknown | 2 | 13% |
Attention Score in Context
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#22,760,732
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