The effect of ABCB1 polymorphism on sirolimus in renal transplant recipients: a meta-analysis

Abstract

Background: Sirolimus (SRL) is an immunosuppressive drug and substrate of the P-glycoprotein (P-GP) encoded by ABCB1. The relationship between ABCB1 polymorphism and the pharmacokinetics of SRL in different studies were conflicting in renal transplant recipients. Thus, this meta-analysis aims to investigate the influence of ABCB1 C3435T, C1236T, and G2677T/A polymorphisms on the dose-adjusted trough level (C/D) of SRL in renal transplant recipients.Methods: PubMed, Embase, and the Cochrane Library were searched for relevant studies. The quality of each eligible study was assessed according to Newcastle-Ottawa Scale. The STATA 15.0 was adopted to perform the meta-analysis. The fixed-effects model was used for pooled results with low heterogeneity (I 2 ≤50%); otherwise, the random-effects model was used.Results: A total of 6 studies were included in the meta-analysis. Results of pooled analysis showed no significant association of SRL C/D ratio with ABCB1 C3435T polymorphism. The subgroup analysis based on different ethnic groups and different time-points after SRL initiation in renal transplant recipients were also conducted. No significant association was observed in these subgroups. Significant associations were showed between ABCB1 C1236T polymorphism and the C/D ratio of SRL in the homozygous model

Nutritional reprogramming of mouse liver proteome is dampened by metformin, resveratrol, and rapamycin

“…Metformin, rapamycin, and resveratrol did not influence intake of macronutrients (Figure S1B). Blood levels for metformin, rapamycin, and resveratrol were not influenced by energy density (Figure 1A) and were at or above levels reported in humans administered these drugs (Chimento et al, 2019;Kajbaf et al, 2016;Shao et al, 2020).…”

Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants

“…Hence, their impact on the serum concentrations of drugs effluxed by these transporters is variable. A recent meta-analysis confirmed a reduced dosing requirement for sirolimus in patients with homozygous mutants of ABCB1 1236 C > T [ 35 ]. On the contrary, Llaudo et al did not observe any significant impact of the p-glycoprotein polymorphisms on either sirolimus or tacrolimus but was negatively correlated with cyclosporine concentrations [ 36 ].…”

Sirolimus Pharmacokinetics Variability Points to the Relevance of Therapeutic Drug Monitoring in Pediatric Oncology

“…Sirolimus is extensively metabolized by intestinal and hepatic CYP3A4 and is also a substrate of the p-glycoprotein efflux pump [ 22 , 23 , 32 ]. In literature, administration of strong inhibitors of CYP3A4 such as azoles or diltiazem increases sirolimus trough concentrations [ 21 ], as does the co-administration of cyclosporine, a substrate and inhibitor of the p-glycoprotein [ 33 ].…”

“…Sirolimus is known to be a substrate for both cytochrome P-450 (CYP3A4) and p-glycoprotein [ 20 , 21 ]. Therefore, hepatic dysfunction and co-administration of inducers/inhibitors of CYP3A4 or p-glycoprotein influence the pharmacokinetics of sirolimus [ 22 , 23 ].…”