title: Delayed trough level measurement with the use of prolonged-release tacrolimus.
abstract: Trough concentrations of prolonged-release tacrolimus are usually measured at 24 h after taking the drug in the morning. It is impractical to measure these trough concentrations in patients who visit the outpatient clinic in the afternoon. Trough concentrations obtained in the afternoon may also be suitable for estimating the 24-h exposure. We therefore aimed to assess the usefulness of tacrolimus concentrations measured at 32 h postdose for therapeutic drug monitoring in renal transplant patients who take prolonged-release tacrolimus. We measured tacrolimus pharmacokinetics in 26 patients using prolonged-release tacrolimus. Eleven blood samples were taken during a period of 32 h after ingestion by use of a validated dried blood spot method. Tacrolimus concentrations were measured with HPLC-tandem mass spectrometry. The mean concentrations at 24 and 32 h postdose were 8.3 μg/l (7.5-9.1) and 6.7 μg/l (6.1-7.4), respectively (P < 0.0001). The Spearman correlation coefficients between these concentrations and 24-h exposure were 0.83 and 0.82, respectively (both P < 0.01). In conclusion, delayed trough level measurement provides lower values and therefore requires adjustment of the target range. However, levels measured until 32 h after ingestion remain strongly correlated with 24-h exposure. This warrants the use of delayed trough level measurement to improve patient convenience.
authors.affiliation: Department of Nephrology, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Gerben A J
authors.initials: GA
authors.lastname: van Boekel
authors.forename: Rob E
authors.initials: RE
authors.lastname: Aarnoutse
authors.forename: Karin E J
authors.initials: KE
authors.lastname: Hoogtanders
authors.forename: Thomas R A
authors.initials: TR
authors.lastname: Havenith
authors.forename: Luuk B
authors.initials: LB
authors.lastname: Hilbrands
mesh_terms: D000284:Administration, Oral; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: kidney transplantation; prolonged-release tacrolimus; therapeutic drug monitoring