title: Cyclosporine A does not alter ultrasonic indices of renal blood flow: a potential tool for differentiating toxicity from acute rejection?
abstract: The narrow therapeutic window of cyclosporine A (CsA) means its use is controlled by pharmacokinetic monitoring. However, pharmacokinetics do not always reflect the functional effects of a drug--its pharmacodynamics, such as vasoconstriction. We developed a technique for measuring renal blood flow and used a pig model to determine whether CsA-induced renal vasoconstriction could be detected, thus offering a tool for pharmacodynamic therapeutic drug monitoring. This has been shown to differentiate acute rejection from acute tubular necrosis. Power Doppler intensitometry was used to assess relative vascular volume, and the renal arteriovenous transit time was determined with an intravenous microbubble bolus. Measurements were taken before and at intervals after an intravenous bolus of CsA (10 mg/kg). There was no correlation between index and CsA concentration. Lack of detectable effect after CsA administration to high concentrations suggests that this technique may be able to differentiate CsA toxicity from acute rejection.
authors.affiliation: Department of Immunology, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Herbert
authors.forename: Madeleine
authors.initials: M
authors.lastname: Lynch
authors.forename: Finn
authors.initials: F
authors.lastname: Morgan
authors.forename: Ivan
authors.initials: I
authors.lastname: Berton
authors.forename: Robert
authors.initials: R
authors.lastname: Eckersley
authors.forename: Gordon
authors.initials: G
authors.lastname: Williams
authors.forename: Martin
authors.initials: M
authors.lastname: Blomley
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Warrens
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D006084:Graft Rejection / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D023421:Models, Animal; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D016572:Cyclosporine