The Study On Pharmacokinetics Of Clarithromycin In Human Body And Interaction With Lansoprazole In Rat Plasma And Mice Tissue

1. Studies of Relative Bioavailability of Clarithromy cin Sustained-Release CapsuleOBJECTIVE To establish a LC/MS/MS method for determination of clarithromycin in human plasma and to study pharmacokinetics and relative bioavailability of clarithromycin sustained-release capsule and clarithromycin sustained-release tablet on sell. METHODS The tested drug and internal standard roxithromycin were extracted from plasma samples by ether-dichloromethane(3:2) and chromatgraphed on a C18 column. The mobile phase consisted of methanol-water-formic acid (80:20:0.05).Detection was performed on a triple quadrupole tandem mass spectrometer via electrospray ionization source(ESI) in the positive mode. Selected ion monitoring ions were 748.8/158.1 for clarithromycin and 837.6/158.1 for roxithromycin. RESULTS The linear calibration curves were obtained in the concentration range of 10.0～4000 ng-mL-1. The intra-and inter-run precisions were lower than 15% in terms of relative standard deviation. Pharmacokinetic parameters of the two products after dose of 0.5g clarithromycin to 18 volunteers were as follows:single dose Tmax, Cmax, t1/2,AUC0-t, AUC0-∞, Cl and Vd/F values were found to be (5.36±1.14) and (5.25±0.88) h, (1218±433) and(1333±370)ng·mL-1,(4.59±1.67)and(4.24±2.10)h,(8239±1 553)and(8467±1364)ng·h·mL-1,( 8662±1829)and(8795±1331)ng·h·mL-1,(60.9±15.1)and(58.9±11.3)L·h-1,(382±103)and(366±22 4)L, respectively; multiple dose Tmax, CSSmax, CSSmin, Cav,AUCss and DF values were found to be (5.31±1.11) and (5.28±0.96) h, (1387±396) and (1488±401) ng·mL-1,(64.6±26.8) and (70.1±30.0) ng·mL-1, (399±99.2) and (410±107) ng·mL-1, (9585±2382) and (9830±2578) ng·h·mL-1, (3.32±0.62) and (3.49±0.66) respectively. The relative bioavailability of the test drug for single dose and multiple doses were 98.2±16.3% and 99.5±19.0%. CONCLUSION This method is fast, sensitive and accurary.There is no difference between the test and the reference drugs of clarithromycin in the relative bioavailability (P>0.05). 2. Studies of pharmacokinetic differences of Clarithromycin after co-administered with Lansoprazole in rat plasma and mice tissueOBJECTIVE Establish a LC/MS/MS method for determination of clarithromycin in rat plasma and mice tissue,to study the pharmacokinetic differences of clarithromycin between taking single clarithromycin and together with lansoprazole in rat plasma and mice tissue.METHODS The tested drug and internal standard roxithromycin were extracted from plasma samples and mice tissues by ether-dichloromethane(3:2) and chromatgraphed on a C18 column.The mobile phase consisted of methanol-water-formic acid (90:10:0.05).Detection was performed on a triple quadrupole tandem mass spectrometer via electrospray ionization source(ESI) in the positive mode. Selected ion monitoring ions were 748.9/158.0 for clarithromycin and 837.9/158.0 for roxithromycin. RESULTS The linear calibration curves were obtained in the concentration range of 10～10000 ng-mL"1 in rat plasma. The intra-and inter-run precisions were lower than 15% in terms of RSD.The stability of clarithromycin was very well.The process of clarithromycin in rat are both suitable for two-compartment model.The pharmacokinetic parameters of clarithromycin in rat plasma between taking single clarithromycin and together with lansoprazole were evaluated by Paired-Samples T Test. No significant difference was found on Cmax and Tmax. But after co-administered with lansoprazole, MRT(0-t) is longer, and AUC(0-t) increased. The linear calibration curves were obtained in the concentration range of 40～16000ng·g-1 in mice tissue. AUC of clarithromycin after co-administration in stomach,small intestine,liver and kindey were all higher than those single administration. When co-administration:stomach> small intesine> liver>kindey;single administration:kindey>stomach>liver>small intesine. CONCLUSION This method is stable and accurary.The pharmacokinetic process of clarithromycin in rat can be changed after co-administered with lansoprazole.3. Studies of pharmacokinetic differences of Lansoprazole after co-administered with Clarithromycin in rat plasma and mice tissueOBJECTIVE Establish a HPLC method for determination of lansoprazole in rat plasma and mice tissue,to study the pharmacokinetic differences of lansoprazole between taking single lansoprazole and together with clarithromycin in rat plasma and mice tissue.METHODS Tinidazole was used as internal standard and the samples were extracted by ether-dichloromethane(3:2), The separation was carried out on a C18 column using a mobile phase consisting of 0.2%triethylamine acetonitrile-water (36 :64) pH9.0 at 0.7mL·min-1.RESULTS The linear calibration curves were obtained in the concentration range of 20～20000 ng-mL-1 in rat plasma. The intra-and inter-run precisions were lower than 15% in terms of RSD. The pharmacokinetic parameters of lansoprazole in rat plasma between taking single lansoprazole and together with clarithromycin were evaluated by Paired-Samples T Test. No significant difference was found on Cmax and Tmax.But when co-adiminstration t1/2, MRT(o-t) and MRT(0-∞) were significantly increased.The AUC of lansoprazole was 1.5 times higher than single administration,increasing the bioavailability. The linear calibration curves were obtained in the concentration range of 0.2～100μg·g-1 in mice tissue. AUC of lansoprazole after co-administration in stomach,small intestine,liver and kindey were all higher than those single administration. When co-administration:stomach>smallintesine>liver>kindey;single admin-istration:stomach> small intesine>kindey> liver. CONCLUSION This method is sensitive and stable. The pharmacokinetic process of lansoprazole in rat can be changed after co-administered with clarithromycin.