TY - JOUR
T1 - Stability, human blood distribution and rat tissue localization of promazine and desmonomethylpromazine
AU - Hu, Oliver Y‐P
AU - Curry, Stephen H.
PY - 1989/1/1
Y1 - 1989/1/1
N2 - The stability in human blood and urine, partitioning into red blood cells and plasma protein binding of promazine and desmonomethylpromazine were investigated. Tissue localization was investigated in rats. Promazine and desmonomethylpromazine were stable in human plasma and urine for at least 64 days at −20°. The percentage of promazine not bound to protein in plasma was 10·4 ± 2·43 as estimated by equilibrium dialysis with correction for volume shift, and 11·6 ± 0·43 per cent as estimated by ultracentrifugation. Data for the mean plasma/red blood cell concentration ratio and the red blood cell/plasma distribution coefficient for promazine were 1·19 ± 0·13 and 8·21 ± 0·40, respectively. There was no evidence of time‐dependence in plasma/red blood cell partitioning. Ten rat organs and tissues were examined. The concentrations of promazine and desmonemethylpromazine were highest in lung. For promazine, the rank order of tissue localization was lung > liver > kidney > intestine > brain > spleen > red blood cell > voluntary muscle > plasma > stomach > heart. For desmonomethylpromazine, the order was reversed in the cases of spleen and brain and interchanged in the cases of stomach and muscle. The brain/plasma concentration ratios for promazine and desmonomethylpromazine in rat were 4·69 and 3·87, respectively.
AB - The stability in human blood and urine, partitioning into red blood cells and plasma protein binding of promazine and desmonomethylpromazine were investigated. Tissue localization was investigated in rats. Promazine and desmonomethylpromazine were stable in human plasma and urine for at least 64 days at −20°. The percentage of promazine not bound to protein in plasma was 10·4 ± 2·43 as estimated by equilibrium dialysis with correction for volume shift, and 11·6 ± 0·43 per cent as estimated by ultracentrifugation. Data for the mean plasma/red blood cell concentration ratio and the red blood cell/plasma distribution coefficient for promazine were 1·19 ± 0·13 and 8·21 ± 0·40, respectively. There was no evidence of time‐dependence in plasma/red blood cell partitioning. Ten rat organs and tissues were examined. The concentrations of promazine and desmonemethylpromazine were highest in lung. For promazine, the rank order of tissue localization was lung > liver > kidney > intestine > brain > spleen > red blood cell > voluntary muscle > plasma > stomach > heart. For desmonomethylpromazine, the order was reversed in the cases of spleen and brain and interchanged in the cases of stomach and muscle. The brain/plasma concentration ratios for promazine and desmonomethylpromazine in rat were 4·69 and 3·87, respectively.
KW - Desmonomethylpromazine
KW - Plasma protein binding
KW - Promazine
KW - Red cell participation
KW - Stability
KW - Tissue localization
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U2 - 10.1002/bdd.2510100603
DO - 10.1002/bdd.2510100603
M3 - Article
C2 - 2611355
AN - SCOPUS:0024463440
SN - 0142-2782
VL - 10
SP - 537
EP - 548
JO - Biopharmaceutics & Drug Disposition
JF - Biopharmaceutics & Drug Disposition
IS - 6
ER -