Purpose To determine the relationship between C3435T,a single nucleotide polymorphism (SNP) in exon 26 of the human multidrug
resistant gene (MDR1) and cyclosporine (CsA) pharmacokinetic (PK) parameters among healthy Chinese volunteers. Methods The oral CsA PK study was performed on 20 healthy subjects.Blood CsA concentrations were measured by HPLC and the genotype for the C3435T polymorphism of MDR1 gene was determined by PCR and restriction fragment length polymorphism analysis.The results were further confirmed by sequencing. Results There were 5 homozygous CC,11 heterozygous CT,and 4 homozygous TT
genotypes in these 20 healthy volunteers.According to their genotypes,the mean c max,mean CL/F and mean AUC 0-inf was (2 124.4±179.4) ng/mL,(37.0±6.5) L/h and (13 922.2±2 881.9) ng·h/mL in CC group,(1 934.3±372.8) ng/mL,(45.0±9.0) L/h and (11 511.8±2 192.1) ng·h/mL in CT group,(1 765.3±416.0) ng/mL,(59.5±8.1) L/h and ( 8 515.3±1 062.3) ng·h/mL in TT group,respectively.According to the results,c max and AUC 0-inf in CC and CT group were 15% and 49% larger than those in TT group,while CL/F in CC and CT group was 31% less than those in TT group.There was significant statistical difference between CL/F,AUC 0-inf and genotypes(P=0.013),while there was no statistical difference between c max and genotypes (P>0.05). Conclusions The MDR1 C3435T genotype offers a potential mechanistic basis to explain inter-subject difference in CsA oral bioavailability.