Abstract
Plasma drug concentrations are generally considered to reflect efficacy and pharmacokinetics more directly than those in whole blood. However, whole blood has been selected as the matrix to monitor concentrations of tacrolimus (FK506), because it is difficult to accurately measure plasma FK506 concentrations. Because FK506 highly and saturably binds in blood cells, a change in hematocrit value (Hct) may affect FK506 pharmacokinetics. Therefore, we investigated effects of Hct on FK506 pharmacokinetics. First, we analyzed data on FK506 distribution among human blood cells in vitro. Briefly, we employed an equation, which describes saturable binding of FK506 to blood cells, and simulated plasma FK506 concentrations and clearances using the above equation with respect to a variable Hct. Subsequently, we retrospectively analyzed dosages and whole blood FK506 concentrations to predict plasma FK506 concentrations in living donor transplant recipients. In the simulation study, the Hct changed plasma FK506 concentrations and clearances based in whole blood. In living donor liver transplant recipients, whole blood FK506 concentrations were maintained within a therapeutic range, while the Hct varied after transplantation. The correlation ...Continue Reading
References
Jun 1, 1990·Transplantation·G EirasA Zeevi
Jan 1, 1980·Therapeutic Drug Monitoring·M Rowland
Feb 27, 1994·Transplantation·L BäckmanG Klintmalm
Jun 19, 1998·Therapeutic Drug Monitoring·J M TredgerC E Gonde
Citations
Feb 18, 2011·European Journal of Clinical Pharmacology·Itziar OteoRosario Calvo
Sep 26, 2012·Therapeutic Drug Monitoring·Songmao ZhengMary F Hebert
Jun 4, 2008·Biological & Pharmaceutical Bulletin·Takashi TomitaYukinao Kohda
Oct 6, 2012·Biological & Pharmaceutical Bulletin·Noriyasu FukuokaHitoshi Houchi
Nov 19, 2010·Bioanalysis·Philip Denniff, Neil Spooner
Jan 27, 2016·Expert Opinion on Drug Metabolism & Toxicology·Mi LiRaman Venkataramanan
Sep 25, 2014·Mass Spectrometry Reviews·Michel WagnerGérard Hopfgartner
Jun 24, 2009·Transplantation Proceedings·R YamazakiS Okamoto
Oct 27, 2011·Biopharmaceutics & Drug Disposition·Hisakazu OhtaniAmin Rostami-Hodjegan
Mar 27, 2013·British Journal of Clinical Pharmacology·Songmao ZhengMary F Hebert
Apr 8, 2015·British Journal of Clinical Pharmacology·Carlos Orlando Jacobo-CabralIñaki F Trocóniz
Apr 10, 2016·European Journal of Drug Metabolism and Pharmacokinetics·Ahmed NaderKyle John Wilby
Nov 22, 2014·Pediatric Transplantation·Jane A DickersonRhona M Jack
Apr 9, 2011·Clinica Chimica Acta; International Journal of Clinical Chemistry·Massimo TempestilliLeopoldo P Pucillo
Jun 21, 2016·Transplantation Proceedings·S LimsrichamrernW Dumronggittigule
Jul 25, 2018·Pharmacogenomics·Wan ZhuXiaohua Wei
Aug 4, 2006·Therapeutic Drug Monitoring·Kimberly L Napoli
Sep 28, 2018·Basic & Clinical Pharmacology & Toxicology·Juan Eduardo Reséndiz-GalvánSilvia Romano-Moreno
Apr 16, 2015·International Surgery·Hisashi NakayamaAkiko Kuronuma
Jun 7, 2012·Cancer Chemotherapy and Pharmacology·Mark StrohMarian Iwamoto
Oct 18, 2012·Clinical Pharmacology and Therapeutics·S ZhengK E Thummel
Jan 1, 2013·Transplantation·Mary F HebertThomas R Easterling
Apr 17, 2020·European Journal of Hospital Pharmacy. Science and Practice·Naoki YoshikawaRyuji Ikeda
Apr 29, 2020·International Journal of Clinical Pharmacy·Masashi UchidaItsuko Ishii
Feb 1, 2012·Cancer Chemotherapy and Pharmacology·Mark StrohMarian Iwamoto
Mar 28, 2019·Pediatric Transplantation·Charlotte DefrancqAgnieszka Prytuła
Aug 11, 2012·Cancer Chemotherapy and Pharmacology·Richard M LushAnthony Tolcher
Jun 26, 2021·International Journal of Hematology·Min ZhanFeiqiu Wen