Pharmacokinetics and pharmacodynamics of gliclazide in Caucasians and Australian Aborigines with type 2 diabetes
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Aims Gliclazide pharmacokinetics and pharmacodynamics were assessed in 9 Caucasians and 10 Australian Aborigines with uncomplicated type 2 diabetes. Methods Subjects were on a stable dose of 80 mg gliclazide twice daily, took 160 mg on the morning of study and had a standard breakfast. No further gliclazide was given over the next 48 h. Regular blood samples were drawn for serum glucose, insulin and gliclazide assay. Gliclazide was measured using h.p.l.c. Noncompartmental analysis was used to describe primary data. A multicompartment model incorporating entero‐hepatic recirculation was fitted to group mean serum gliclazide profiles. Results The Caucasians were older than the Aborigines (mean ± s.d. age 53.4 ± 12.2 vs 40.3 ± 6.9 years, P < 0.05) but had similar diabetes duration, body mass index and glycated haemoglobin. Noncompartmental analysis revealed no between‐group differences in gliclazide kinetics. Post‐breakfast serum glucose and insulin responses were also similar apart from a longer time to maximum concentration (tmax) for glucose amongst the Aborigines (2.6 ± 0.4 vs 2.2 ± 0.3 h in Caucasians; P = 0.024). Gliclazide tmax exhibited a skewed unimodal distribution and was not associated with gliclazide maximum concentration, or glucose or insulin responses. Most patients had a serum gliclazide profile suggestive of enterohepatic recirculation and/or biphasic absorption. Model‐derived estimates of the extent of putative enterohepatic recirculation were 30% and 20% of dose in Caucasians and Aborigines, respectively. Conclusions Gliclazide is equally effective in Caucasian and Aboriginal diabetic patients. The pharmacokinetics of oral gliclazide appear more complex than previously thought. Gliclazide pharmacodynamics are unrelated to rate and extent of absorption, consistent with a threshold concentration for hypoglycaemic effect.
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The risk of hypoglycemia of each sulfonylurea relates to its pharmacokinetic properties and is highest with long-acting sulfonylureas such as chlorpropamide, glyburide (glibenclamide), and long-acting glipizide.
“The risk of hypoglycemia of each sulfonylurea relates to its pharmacokinetic properties (104 -108) and is highest with long-acting sulfonylureas such as chlorpropamide, glyburide (glibenclamide), and long-acting glipizide (101,109 -111).”
From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [106]
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- Authors
- Davis, Daly, Walsh, Ilett, Beilby, Dusci, L. J., & Barrett, P. H. R.
- Affiliations
- The University of Western Australia (AU)
- Harry Perkins Institute of Medical Research (AU)
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2000-03
- Volume
- 49
- Issue
- 3
- Pages
- 223-230
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC2014921
- OpenAlex
- W1516390496
- Cited by
- 75
- References
- 25
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 8 · 2020: 3 · 2019: 1 · 2018: 6 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 4
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- gliclazide, pharmacokinetics, pharmacodynamics, type 2 diabetes, Aboriginal Australians, ethnic differences, enterohepatic circulation, oral glucose tolerance, insulin response, hypoglycemic effect
- MeSH terms
- Adult, Aged, Australia, Blood Glucose, Diabetes Mellitus, Type 2, Female, Gliclazide, Humans, Hypoglycemic Agents, Insulin, Male, Middle Aged, Postprandial Period, White People, Native Hawaiian or Other Pacific Islander
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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