title: Clinical pharmacokinetics of tacrolimus in Iranian liver transplant recipients.
abstract: Tacrolimus, a cornerstone of immunosuppressive therapy in solid organ transplantation, has a narrow therapeutic range with considerable inter-individual and intra-individual pharmacokinetic variability. To date, there is no information on the pharmacokinetics of tacrolimus in Iranian liver transplant recipients. This study was designed to determine pharmacokinetic properties of orally administered tacrolimus in Iranian adult liver transplant recipients. Tacrolimus doses and steady state whole blood trough concentrations as well as patient demographic and clinical data were obtained retrospectively using the 30 included patients' medical records. Pharmacokinetic parameters were estimated by using a nonlinear mixed effect model program (Monolix version 3.1). Absorption rate constant was fixed at two hours(-1). Drug apparent clearance (CL/F), apparent volume of distribution (Vd/F), and elimination half life (t½β) were calculated. The administered dose of tacrolimus to the patients ranged from 0.02 to 0.14 mg/Kg/day. Tacrolimus blood trough concentrations varied widely within the range of 1.8 to 30 ng/mL. The mean values of CL/F, Vd/F, and t½β were found to be 9.3 ± 0.96 L/h, 101 ± 29 L, and 7.5 hours, respectively. The pharmacokinetics of tacrolimus was highly variable among our patients. CL/F, Vd/F, and t½β of tacrolimus in this study were comparable to reported values from Italian heart transplant patients but somewhat different from reported ones from other solid organ transplant populations.
authors.affiliation: Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Nasiri-Toosi
authors.affiliation: Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Simin
authors.initials: S
authors.lastname: Dashti-Khavidaki
authors.affiliation: Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Nasiri-Toosi
authors.affiliation: Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Jafarian
authors.affiliation: Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Khalili
authors.affiliation: Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Shirinsadat
authors.initials: S
authors.lastname: Badri
authors.affiliation: Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sima
authors.initials: S
authors.lastname: Sadrai
keywords: Liver transplantation; Pharmacokinetics; Tacrolimus
references.citation: Clin Pharmacokinet. 1995 Dec;29(6):404-30
references.pmid: 8787947
references.citation: Clin Chem. 1997 Nov;43(11):2189-90
references.pmid: 9365410
references.citation: Transplant Proc. 2009 Apr;41(3):840-2
references.pmid: 19376366
references.citation: Ther Drug Monit. 2005 Aug;27(4):422-30
references.pmid: 16044097
references.citation: Exp Clin Transplant. 2012 Dec;10(6):586-91
references.pmid: 22770208
references.citation: Clin Pharmacokinet. 2001;40(4):283-95
references.pmid: 11368293
references.citation: Iran J Pharm Res. 2013 Summer;12(3):547-56
references.pmid: 24250661
references.citation: Clin Pharmacol Ther. 2002 Dec;72(6):660-9
references.pmid: 12496747
references.citation: Clin Pharmacokinet. 2006;45(1):59-75
references.pmid: 16430311
references.citation: Liver Transpl. 2003 Feb;9(2):130-7
references.pmid: 12548506
references.citation: Ther Drug Monit. 1999 Feb;21(1):2-7
references.pmid: 10051048
references.citation: Br J Clin Pharmacol. 2007 Dec;64(6):750-7
references.pmid: 17425625