Stereoselective binding of chiral anti-diabetic drug nateglinide to plasma proteins
-
Srinivas Maddi
,
Gerhard Scriba
Abstract
The binding of nateglinide (NA) enantiomers with human plasma (HP), human serum albumin (HSA) and bovine serum albumin (BSA) was investigated. The protein binding was studied over a drug concentration range of 5–100 μM at a protein concentration of 600 μM. Unbound drug concentrations were determined by direct chiral liquid chromatography using chiralcel OJ-RH column. At therapeutic drug concentrations, the protein binding of each enantiomer was >98%. The results showed that the binding of NA enantiomers was stereoselective, mutually competitive and non-linear. The binding characteristics were, however, opposite for the two most important plasma binding proteins. Opposite stereo-selectivity was observed between BSA and HSA while stereo-selectivity was identical between HSA and HP. Scatchard analysis was used to illustrate the different binding affinities of NA enantiomers to BSA, HSA and HP. The interaction between enantiomers observed in HP and serum albumins was confirmed as a competitive type interaction at the high affinity site. Scatchard analysis was used to illustrate the different binding affinities of NA enantiomers to BSA, HSA and HP.
©2011 by Walter de Gruyter Berlin Boston
Articles in the same Issue
- Editorial
- Ageing populations, complex diseases and their challenge to 21st century healthcare: the focus of the European Society for Pharmacogenomics and Theranostics
- Reviews
- Clopidogrel pharmacogenetics: metabolism and drug interactions
- Drug interactions in African herbal remedies
- Minireview
- Experimental evidence of the potential use of erythropoietin by intranasal administration as a neuroprotective agent in cerebral hypoxia
- Original Articles
- A comparison of simple allometric and maturation models for the prediction of morphine clearance in pediatrics
- Rhabdomyolysis-induced acute renal failure due to itraconazole and simvastatin association
- Stereoselective binding of chiral anti-diabetic drug nateglinide to plasma proteins
- Abstracts
- 4th BBBB – Bled International Conference on Pharmaceutical Sciences
Articles in the same Issue
- Editorial
- Ageing populations, complex diseases and their challenge to 21st century healthcare: the focus of the European Society for Pharmacogenomics and Theranostics
- Reviews
- Clopidogrel pharmacogenetics: metabolism and drug interactions
- Drug interactions in African herbal remedies
- Minireview
- Experimental evidence of the potential use of erythropoietin by intranasal administration as a neuroprotective agent in cerebral hypoxia
- Original Articles
- A comparison of simple allometric and maturation models for the prediction of morphine clearance in pediatrics
- Rhabdomyolysis-induced acute renal failure due to itraconazole and simvastatin association
- Stereoselective binding of chiral anti-diabetic drug nateglinide to plasma proteins
- Abstracts
- 4th BBBB – Bled International Conference on Pharmaceutical Sciences
