BACKGROUND: Physiologic functions that may affect pharmacokinetics of drugs are altered in elderly patients. The current study was performed to elucidate the effect of age on cyclosporine A (CsA) pharmacokinetics in renal transplant recipients. METHOD: Twenty-five renal transplant recipients on CsA treatment were included in the study. CsA doses were adjusted by C2 monitoring. The patients were divided into two groups based on age; elderly: more than 65 years (n=11, mean 73 years) and younger: 18 to 64 years (n=14, mean 43 years). A full 12-hr pharmacokinetic profile was performed during stable phase. CsA whole blood and intracellular T-lymphocytes concentrations (first 6 hr) were measured. Genotyping of the CYP3A5*1/*3 and ABCB1 (C1236T, G2677T, C3435T) polymorphisms and quantification of whole blood mRNA ABCB1 expression were performed in all patients. RESULTS: Elderly patients achieved target C2 levels with lower CsA doses than the younger patients (4.3+/-0.8 vs. 6.1+/-2.1 mg/day/kg, P=0.025) because of lower clearance of CsA (22.7+/-5.1 vs. 30.5+/-11.1 L/hr, P=0.031). Elderly patients also showed 44% higher intracellular-to-whole blood CsA ratio than younger patients (P=0.02). Neither the CYP3A5*1, the ABCB1 genotypes nor mRNA ABCB1 expression revealed any significant influence on CsA pharmacokinetics. CONCLUSION: The clearance of CsA decreased with increasing age. In addition, elderly patients had a significant larger proportion of the whole blood CsA concentration located at the site of action (within T lymphocytes). This indicates that in elderly recipients it might be safe to aim for an even lower whole blood target levels than current guidelines propose.
BACKGROUND: Physiologic functions that may affect pharmacokinetics of drugs are altered in elderly patients. The current study was performed to elucidate the effect of age on cyclosporine A (CsA) pharmacokinetics in renal transplant recipients. METHOD: Twenty-five renal transplant recipients on CsA treatment were included in the study. CsA doses were adjusted by C2 monitoring. The patients were divided into two groups based on age; elderly: more than 65 years (n=11, mean 73 years) and younger: 18 to 64 years (n=14, mean 43 years). A full 12-hr pharmacokinetic profile was performed during stable phase. CsA whole blood and intracellular T-lymphocytes concentrations (first 6 hr) were measured. Genotyping of the CYP3A5*1/*3 and ABCB1 (C1236T, G2677T, C3435T) polymorphisms and quantification of whole blood mRNA ABCB1 expression were performed in all patients. RESULTS: Elderly patients achieved target C2 levels with lower CsA doses than the younger patients (4.3+/-0.8 vs. 6.1+/-2.1 mg/day/kg, P=0.025) because of lower clearance of CsA (22.7+/-5.1 vs. 30.5+/-11.1 L/hr, P=0.031). Elderly patients also showed 44% higher intracellular-to-whole blood CsA ratio than younger patients (P=0.02). Neither the CYP3A5*1, the ABCB1 genotypes nor mRNA ABCB1 expression revealed any significant influence on CsA pharmacokinetics. CONCLUSION: The clearance of CsA decreased with increasing age. In addition, elderly patients had a significant larger proportion of the whole blood CsA concentration located at the site of action (within T lymphocytes). This indicates that in elderly recipients it might be safe to aim for an even lower whole blood target levels than current guidelines propose.
Authors: Christopher D Blosser; Ari Huverserian; Roy D Bloom; Peter D Abt; Simin Goral; Arwin Thomasson; Justine Shults; Peter P Reese Journal: Transplantation Date: 2011-04-27 Impact factor: 4.939
Authors: Jiang-Tao Tang; Brenda C de Winter; Dennis A Hesselink; Ferdi Sombogaard; Lan-Lan Wang; Teun van Gelder Journal: Br J Clin Pharmacol Date: 2016-11-30 Impact factor: 4.335
Authors: Felix Krenzien; Abdallah ElKhal; Markus Quante; Hector Rodriguez Cetina Biefer; Uehara Hirofumi; Steven Gabardi; Stefan G Tullius Journal: Transplantation Date: 2015-11 Impact factor: 4.939