title: Total plasma protein effect on tacrolimus elimination in kidney transplant patients--population pharmacokinetic approach.
abstract: Data from routine therapeutic drug monitoring of 105 adult kidney transplant recipients were used for population pharmacokinetic analysis which was performed using a non-linear mixed-effects modeling. The effect of demographic and clinical factors on tacrolimus clearance was evaluated. Following the initiation of treatment with tacrolimus, the results of our study indicate a decrease of the drug clearance on day 15, 1 and 6 months after transplantation for 4.4%, 6.3% and 10.92%, respectively. Our model suggests a negative correlation between tacrolimus clearance and haematocrit. According to final model, clearance decreases with increasing of aspartate aminotransferase. Our results demonstrated that CL/F increases with patients' weight. This study reveals incensement for 10.4% in tacrolimus clearance with alteration of patients' minimal measured total protein levels to upper normal range. The findings of this study explore various factors of tacrolimus pharmacokinetic variability and point out a relationship between tacrolimus clearance and total plasma protein. Developed model demonstrates the feasibility of estimation of individual tacrolimus clearance and may allow rational individualization of tacrolimus dosing in kidney transplant patients.
authors.affiliation: Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address: bojanap@pharmacy.bg.ac.rs.
authors.forename: Bojana
authors.initials: B
authors.lastname: Golubović
authors.affiliation: Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Vučićević
authors.affiliation: Nephrology Clinic, Clinical Centre of Serbia, University of Belgrade, Pasterova 2, 11000 Belgrade, Serbia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Radivojević
authors.affiliation: Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Sandra Vezmar
authors.initials: SV
authors.lastname: Kovačević
authors.affiliation: Departmant of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Dr. Subotića 1, 11000 Belgrade, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Prostran
authors.affiliation: Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Branislava
authors.initials: B
authors.lastname: Miljković
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D001798:Blood Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D001798:Blood Proteins; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: Kidney transplantation; Plasma proteins; Population pharmacokinetics; Tacrolimus; Therapeutic monitoring