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Optimal dosing of g...
Optimal dosing of gliclazide-A model-based approach
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- Mim, Sabiha R. (författare)
- Uppsala universitet,Institutionen för farmaci,Pharmacometric Research Group
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- Hussein, Haneen (författare)
- Uppsala universitet,Institutionen för farmaci,Pharmacometric Research Group
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- Vidadi, Samira (författare)
- Uppsala universitet,Institutionen för farmaci,Pharmacometric Research Group
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- Leisegang, Rory (författare)
- Uppsala universitet,Institutionen för farmaci,Stellenbosch Univ, Family Ctr Res Ubuntu, Dept Paediat & Child Hlth, Stellenbosch, South Africa.,Pharmacometric Research Group
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- Karamchand, Sumanth (författare)
- Stellenbosch Univ, Div Cardiol, Stellenbosch, South Africa.
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- Rambiritch, Virendra (författare)
- Univ KwaZulu Natal, Discipline Pharmaceut Sci, Durban, South Africa.
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- Cotton, Mark F. (författare)
- Stellenbosch Univ, Family Ctr Res Ubuntu, Dept Paediat & Child Hlth, Stellenbosch, South Africa.
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- Naidoo, Poobalan (författare)
- Univ KwaZulu Natal, Inkosi Albert Luthuli Cent Hosp, Nelson R Mandela Sch Med, Dept Nephrol, Durban, South Africa.
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- Kjellsson, Maria C., docent, 1975- (författare)
- Uppsala universitet,Institutionen för farmaci,Pharmacometric Research Group
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(creator_code:org_t)
- 2023-03-30
- 2023
- Engelska.
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : John Wiley & Sons. - 1742-7835 .- 1742-7843. ; 133:1, s. 59-72
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Gliclazide was approved as a treatment for type 2 diabetes in an era before model-based drug development, and consequently, the recommended doses were not optimised with modern methods. To investigate various dosing regimens of gliclazide, we used publicly available data to characterise the dose-response relationship using pharmacometric models. A literature search identified 21 published gliclazide pharmacokinetic (PK) studies with full profiles. These were digitised, and a PK model was developed for immediate- (IR) and modified-release (MR) formulations. Data from a gliclazide dose-ranging study of postprandial glucose were used to characterise the concentration-response relationship using the integrated glucose-insulin model. Simulations from the full model showed that the maximum effect was 44% of the patients achieving HbA1c <7%, with 11% experiencing glucose <3 mmol/L and the most sensitive patients (i.e., 5% most extreme) experiencing 35 min of hypoglycaemia. Simulations revealed that the recommended IR dose (320 mg) was appropriate with no efficacy gain with increased dose. However, the recommended dose for the MR formulation may be increased to 270 mg, with more patients achieving HbA1c goals (i.e., HbA1c <7%) without a hypoglycaemic risk higher than the resulting risk from the recommended IR dose.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- concentration-response relationship
- gliclazide
- non-linear mixed effects models
- pharmacodynamics
- pharmacokinetics
- pharmacometrics
- type 2 diabetes
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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