ISSN:
1432-1041
Keywords:
Chlorthalidone
;
Hygroton®
;
in vitro
;
human serum albumin binding
;
red blood cell carbonic anhydrase binding
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary The binding of chlorthalidone to human blood components has been studied in vitro. The drug was preferentially taken up by red blood cells, the partition ratio between plasma and the cell fraction being dependent on the drug concentration. When the concentration of chlorthalidone in blood was less than 15–20 µg/ml, more than 98% of the compound was bound to red cells. Increasing the concentration resulted in an abrupt change of the partition ratio in favour of plasma, which indicates a saturable receptor for chlorthalidone in red cells, namely carbonic anhydrase (HCA). The association constant of the drug-enzyme complex KassHCA was 2.76×106 l/mole. For the two major isoenzymes of carbonic anhydrase, HCA-B and HCA-C, the association constants were different: KassHCA-B=2.43×106 l/mole and KassHCA-C=5.69×106 l/mole. The number of binding sites n=1 in all cases. In human serum at 37°C, over a concentration range of 0.02–7.7 µg/ml, 75.7% of chlorthalidone was bound to proteins. The major portion of the binding was to albumin (HSA), the association constant of the complex KassHSA=1.18×103 l/mole and the number of binding sites n=4. The much higher association constant of chlorthalidone with HCA than with HSA can account for selective uptake of the drug by red cells.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00561547
Permalink
