title: Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients.
abstract: Prolonged-release tacrolimus was developed as a once-daily formulation with ethylcellulose as the excipient, resulting in slower release and reduction in peak concentration (Cmax ) for a given dose compared with immediate-release tacrolimus, which is administered twice daily. This manuscript reviews pharmacokinetic information on prolonged-release tacrolimus in healthy subjects, in transplant recipients converted from immediate-release tacrolimus, and in de novo kidney and liver transplant recipients. As with the immediate-release formulation, prolonged-release tacrolimus shows a strong correlation between trough concentration (Cmin ) and area under the 24-hour time-concentration curve (AUC24 ), indicating that trough whole blood concentrations provide an accurate measure of drug exposure. We present the pharmacokinetic similarities and differences between the two formulations, so that prescribing physicians will have a better understanding of therapeutic drug monitoring in patients receiving prolonged-release tacrolimus.
authors.affiliation: Astellas Pharma Global Development, Northbrook, IL, USA.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Tanzi
authors.affiliation: Astellas Pharma Europe Ltd, Surrey, UK.
authors.forename: Nasrullah
authors.initials: N
authors.lastname: Undre
authors.affiliation: Astellas Pharma Global Development, Northbrook, IL, USA.
authors.forename: James
authors.initials: J
authors.lastname: Keirns
authors.affiliation: Astellas Pharma Global Development, Northbrook, IL, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Fitzsimmons
authors.affiliation: Astellas Pharma Global Development, Surrey, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Brown
authors.affiliation: Transplant Genomics Inc., Brookline, MA, USA.
authors.forename: M Roy
authors.initials: MR
authors.lastname: First
mesh_terms: D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D006084:Graft Rejection / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D016377:Organ Transplantation; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D066027:Transplant Recipients
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: pharmacokinetics; tacrolimus prolonged-release