CIMETIDINE role with PROPRANOLOL image isomer of the relationship between
Abstract
As the three-dimensional expansion of chemical knowledge, making isomers of drugs and mirror, or mirror image isomers different secret
Structure property relationship between the role of being
concerned and Ming Liao. There are many reports that cimetidine and (±) -
When propranolol and services, cimetidine can increase significantly (±)- propranolol plasma concentrations, but the cim-
etidine for propranolol Zhi structures for the mirror effect between the impact of the case have yet to be explored was the experiment
The purpose of cimetidine and propranolol isomers mirroring
relationship between the role of whether the three-dimensional Selectivity, and as a reference to the clinical effects of drugs.
To six rabbits as experimental samples, collected interleaved mode of oral cimetidine on experimental oral (100 mg / kg) and
Intravenous injection (3.5 mg / kg) to vote for (±)-propranolol.HCl mirror when cimetidine and propranolol
Isomers, the relationship between the pharmacokinetics.
In this study, HPLC method (ODS column 250x4.6, 58% CH3CN in 0.1%
H3PO4 solution for mobile
Phase, fluorescence detector ex: 295nm, em: 345nm) separation of propranolol and GITC formed by the dia-
stereoisomer derivatives, and this method of production of standard calibration curve to quantify the plasma Inspection of (-) - and (+)-pro-
pranolol concentrations, respectively. The results showed that oral administration of cimetidine at the same time can reduce the (+)- propranolol and (
-)-Propranolol oral clearance (apparent oral clearance, CLoral), respectively, of its lower
For the (+)-propranolol65% (p <0.02) and (-)-propranolol75% (p <0.05), In addition to the (-)/(+
)-Enantiomer ratio of change in CLoral view, it seems that inhibition of metabolism with stereoselectivity
(-)/(+)- Isomer = 0.7585 ± 0.1937 (p <0.05).
In addition to the time of cimetidine with oral propranolol for image isomers influence, but also to extend the vein at the same time
Injection of (±)-propranolol.HCl time (+) - and (-)-propranolol of the half- life, respectively (+)-propra-
nolol extension of 51% (p <0.01), (-)-propranolol to extend the 53% (p
<0.05), and selective increase (+)-p-
ropranolol 21% of the AUC (P <0.01) and lower (+)-propranolol 18% of the plasma clearance rate (plasma c-
learance) (p <0.05).
English Abstract
