title: Lower calcineurin inhibitor doses in older compared to younger kidney transplant recipients yield similar troughs.
abstract: The number of older adults undergoing kidney transplantation has increased, yet little is known about calcineurin inhibitor (CNI) metabolism in this group. We studied CNI troughs and doses to determine if there were age-related differences in metabolism and dose requirements. We studied 348 young (18-34 years), 1831 middle (35-64 years) and 374 older (65-84 years) adult kidney transplant recipients enrolled in a seven-center prospective study. Troughs were obtained from each patient 2×/week in weeks 1-8 and 2×/month in months 3-6. A multivariable linear-mixed model examined the effect of age on log dose and weight normalized troughs. Older recipients had higher normalized tacrolimus troughs than middle or young age adults despite receiving doses a median of 1-2 mg/day lower. Age and CYP3A5*1 genotype had the largest effect on tacrolimus troughs. Older recipients also had higher normalized cyclosporine troughs than middle or young adults despite receiving median doses 100 mg/day lower. After normalization for dose and weight, CNI troughs were more than 50% higher in older adults than young adults. These data support age-related changes in CNI metabolism. Further studies are needed to determine optimal dosing of CNIs in the elderly.
authors.affiliation: Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA. jacob117@umn.edu
authors.forename: P A
authors.initials: PA
authors.lastname: Jacobson
authors.forename: D
authors.initials: D
authors.lastname: Schladt
authors.forename: W S
authors.initials: WS
authors.lastname: Oetting
authors.forename: R
authors.initials: R
authors.lastname: Leduc
authors.forename: W
authors.initials: W
authors.lastname: Guan
authors.forename: A J
authors.initials: AJ
authors.lastname: Matas
authors.forename: A
authors.initials: A
authors.lastname: Israni
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D019703:Calcineurin; D016559:Tacrolimus