| Aims:We investigated whether SLC22A11022C＞T or SLC22A1 848C＞T polymorphism plays a role in the metabolism of ranitidine and whether influence the Pharmacokinetics and Pharmacodynamics of ranitidine in vivo.Methods:Genotypes were determined using the PCR assay for 560 Chinese Han populations' DNA samples.Then 28 volunteers,of whom 10 were SLC22A1 1022CC and SLC22A1 848CC,9 were SLC22A1 1022CT,5 were SLC22A1 1022TT,4 were SLC22A1 848CT,have been selected out to take part in the trial which is carefully designed.On the morning of the trial day,volunteers were randomly grouped,and each were given 300 mg ranitidine,before which a control blood sample were taken 1 hour prior to the adminastration.For ranitidine pharmacokinetics,blood samples were collected at 0.25,0.50,0.75,1.0,1.5,2.0,2.5,3.0,4.0,8.0,12.0,and 24.0 h after the adminastration.Plasma were taken out from the blood with 30 mins after the blood samples were taken,and stored at -20℃for the HPLC analysis.Results:A total of 560 healthy volunteers were genotyped.The allelic frequency of C was 88.2%and T was 11.8%for SLC22A1 1022C＞T.The allelic frequency of C was 99.2%and T was 0.8%for SLC22A1 848C＞T. There is not statistical difference between ethnics.Both SLC22A11022C＞T and SLC22A1 848C＞T genotype were taken into the consideration whether they have a significant effect on the pharmacokinetics of ranitidine.According to this experiment,we get to know that the polymorphism of SLC22A11022C＞T could influence the PK value of ranitidine significantly:The SLC22A11022CC group has a smaller Cmax,AUC(0-t),AUC0-∞ of ranitidine than SLC22A11022TT group does,and the SLC22A11022CT group has a smaller AUC(0-t),AUC0-∞ than SLC22A11022TT group does.There is no difference between SLC22A1 848CC and SLC22A1 848C＞T group.Conclusions:The polymorphism of SLC22A1 1022C＞T could influence the PK value of ranitidine,however,there is no evidence from this experiment the the polymorphism of SLC22A1 848C＞T could influence the PK value of ranitidine. |
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