scholarly journals Associations of ABCB1, NFKB1, CYP3A, and NR1I2 polymorphisms with cyclosporine trough concentrations in Chinese renal transplant recipients

2013 ◽  
Vol 34 (4) ◽  
pp. 555-560 ◽  
Author(s):  
Yu Zhang ◽  
Jia-li Li ◽  
Qian Fu ◽  
Xue-ding Wang ◽  
Long-shan Liu ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Trough Concentrations

Steady-state concentration of cyclosporin G (OG37-325) and its metabolites in renal transplant recipients

1994 ◽  
Vol 40 (4) ◽  
pp. 613-616 ◽  
Author(s):  
L J Langman ◽  
A B Leichtman ◽  
W F Weitzel ◽  
R W Yatscoff
Keyword(s):  
Steady State ◽  
Renal Transplant ◽  
Secondary Metabolites ◽  
Whole Blood ◽  
Relative Concentration ◽  
Cross Reactivity ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Dosing Interval ◽  
Trough Concentrations

Abstract The steady-state concentrations of cyclosporin G (OG37-325) (CsG) and six of its metabolites (GM1, GM9, GM4N, GM1c, GM1c9, GM19) were measured throughout the 12-h dosing interval in six renal transplant recipients receiving CsG as prophylaxis against acute cellular rejection. The mean 12-h whole-blood trough concentrations (micrograms/L) were CsG, 131 +/- 26; GM1, 79 +/- 55; GM9, 110 +/- 114; GM4N, 28 +/- 18; GM1c, 31 +/- 18; GM1c9, 216 +/- 145; and GM19, 303 +/- 217. The relative concentration of the primary metabolites (GM1, GM9, GM4N) remained stable with respect to CsG throughout the dosing interval, whereas that of the secondary metabolites increased. The secondary metabolites GM19 and GM1c9 exhibited extensive between-patient variation. We investigated the effect of these metabolites on commercially available monoclonal antibody-based fluorescence polarization immunoassays (FPIA) and RIAs adapted for measurement of CsG. The 12-h whole-blood trough concentrations measured by FPIA and RIA exceed those measured by HPLC by 19% and 36%, respectively. These measured biases corresponded closely with the calculated biases (FPIA 19%, RIA 28%) based on the known cross-reactivities of CsG metabolites and their concentrations. These results suggest that cross-reactivity with metabolites account for a large part of the bias observed in immunoassays of CsG.

scholarly journals No Influence of the MDR-1 C3435T Polymorphism or a CYP3A4 Promoter Polymorphism (CYP3A4-V Allele) on Dose-adjusted Cyclosporin A Trough Concentrations or Rejection Incidence in Stable Renal Transplant Recipients

2001 ◽  
Vol 47 (6) ◽  
pp. 1048-1052 ◽  
Author(s):  
Nicolas von Ahsen ◽  
Michael Richter ◽  
Clemens Grupp ◽  
Burckhardt Ringe ◽  
Michael Oellerich ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Cyclosporin A ◽  
Promoter Polymorphism ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
C3435t Polymorphism ◽  
Trough Concentrations ◽  
Cyp3a4 Enzyme ◽  
Mdr 1

Abstract Background: A substantial proportion of the variability in the absorption and clearance of cyclosporin A (CsA) after oral administration has been attributed to variability in liver cytochrome P-450 3A4 (CYP3A4) activity and intestinal P-glycoprotein (P-gp) concentration. A polymorphism in the CYP3A4 promoter region, termed “variant” allele CYP3A4-V, was postulated to be associated with altered CYP3A4 enzyme activity. A polymorphism in exon 26 (C3435T) of the multidrug resistance-1 (MDR-1) gene was correlated with intestinal expression and in vivo activity of P-gp. Methods: We investigated the occurrence of both polymorphisms in 124 stable Caucasian renal transplant recipients (>6 months after transplantation) on CsA as the primary immunosuppressant. Real-time, rapid-cycle PCR methods were developed and used for genotyping. Results: The estimated allele frequencies for the MDR-1 C3435T allele (54%) and the CYP3A4-V allele (4.8%) were similar to those reported for Caucasian populations. No significant differences were found for the CsA doses needed to maintain similar CsA trough concentrations in patients with and without the CYP3A4-V allele or in patients with different MDR-1 C3435T genotypes. Furthermore, neither of the polymorphisms investigated was associated with renal function as assessed by creatinine plasma concentration or, in a retrospective analysis, the incidence of acute rejection. Conclusions: These findings suggest that the MDR-1 C3435T mutation and the CYP3A4-V variant are not major determinants of CsA efficacy in renal transplant recipients.

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