First human trial of FTY720, a novel immunomodulator, in stable renal transplant patients.

Journal of the American Society of Nephrology : JASN
K BuddeHans H Neumayer

Abstract

FTY720 is a novel immunomodulator to be developed for use in organ transplantation. The primary objective of this study was to measure safety, single-dose pharmacokinetics, and pharmacodynamics in stable renal transplant patients-the first human use of FTY720. This study used a randomized, double-blind, placebo-controlled design that explored single oral doses of FTY720 from 0.25 to 3.5 mg in 20 stable renal transplant patients on a cyclosporine-based regimen. Safety assessments and blood samples were taken predose and at multiple time points during a 96-h period postdose. Standard pharmacokinetic parameters were derived from the FTY720 whole blood concentrations, measured by HPLC/MS/MS. FTY720 was well tolerated, with no serious adverse events. Transient, asymptomatic bradycardia occurred after administration in 10 of 24 doses of FTY720. Pharmacokinetics are characterized by a prolonged absorption phase; the terminal elimination phase started 36 h after the administration, with elimination half-life (t(1/2)) ranging from 89 to 157 h independent of dose. Maximum plasma concentration and AUC were proportional to dose with low intersubject variability, the apparent volume of distribution (V(d)/F) ranged from 1116 to 1737 L. FTY p...Continue Reading

References

Apr 9, 1983·British Medical Journal·J V BertouchJ Bradley
May 1, 1994·The Journal of Nutrition·E M SchmelzA H Merrill
Jul 1, 1997·International Journal of STD & AIDS·P J CampbellD Harvey
Jan 1, 1997·Transplant International : Official Journal of the European Society for Organ Transplantation·M MitsusadaM Miyata
Aug 29, 1998·Clinical Biochemistry·P Troncoso, B D Kahan
Jul 8, 1999·The Journal of Nutrition·H VesperA H Merrill
May 23, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·D D PinschewerR M Zinkernagel
Sep 26, 2001·Transplantation·V BrinkmannS Chen

❮ Previous
Next ❯

Citations

Mar 12, 2015·Progress in Transplantation : Official Publication, North American Transplant Coordinators Organization ... [et Al.]·Badri ShresthaAndrew Raftery
Jan 17, 2013·Multiple Sclerosis : Clinical and Laboratory Research·Masami TanakaKeiko Tanaka
Feb 27, 2021·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Martina Petruzzo, Roberta Lanzillo
Dec 25, 2002·Trends in Pharmacological Sciences·Dong Soon Im
Dec 17, 2002·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Flavio Vincenti
May 10, 2003·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Zandong YangKevin R Lynch
Aug 28, 2003·Current Opinion in Chemical Biology·Hugh Rosen, Jiayu Liao
May 13, 2004·The Annals of Pharmacotherapy·John M KovarikAlice B Gottlieb
Oct 22, 2003·Journal of Hepatology·Filomena ContiYvon Calmus
Sep 13, 2003·Immunological Reviews·Hugh RosenChristopher Alfonso
Nov 5, 2003·FEBS Letters·Steven W PaughSarah Spiegel
Jan 13, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Markus H Gräler, Edward J Goetzl
Apr 13, 2004·Transplantation·Martin WijkstromBernhard J Hering
Feb 12, 2004·Kidney International·Duska DragunHans-Hellmut Neumayer
Mar 26, 2004·Transplantation Proceedings·D DragunH H Neumayer
Mar 26, 2004·Transplantation Proceedings·R Ferguson
Apr 6, 2004·Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]·Sylvie EuvrardNicole Lefrancois
Apr 23, 2004·Journal of Clinical Pharmacology·John M KovarikThomas Hunt
May 19, 2004·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Grit SchroederManfred Lehmann
May 19, 2004·Immunology·Stefan KrautwaldUlrich Kunzendorf
Jun 25, 2016·Circulation Research·Danica Petrovic-DjergovicDavid J Pinsky
Jun 5, 2004·Bioorganic & Medicinal Chemistry Letters·Jeffrey J HaleSuzanne Mandala
Jun 17, 2004·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Ulrich KunzendorfDieter Kabelitz
Jul 21, 2004·Journal of the Neurological Sciences·R E Gonsette
Jan 27, 2016·Journal of the Neurological Sciences·Mauricio F Farez, Jorge Correale
Jun 30, 2004·Transplantation·Markus GubaEdward K Geissler
Oct 6, 2004·Pharmacotherapy·Karen L HardingerDaniel C Brennan
Sep 3, 2004·Current Opinion in Immunology·Adam C YoppJonathan S Bromberg
Sep 2, 2004·Biological & Pharmaceutical Bulletin·Takeyuki KohnoTetsuro Fujita
Jun 20, 2003·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Klemens BuddeHans-Hellmut Neumayer
Apr 20, 2004·British Journal of Clinical Pharmacology·John M KovarikGerolf Kraus
Dec 16, 2004·Pediatric Transplantation·Nancy R Krieger, Sukru Emre
Dec 24, 2004·The New England Journal of Medicine·Philip F Halloran
Jan 20, 2005·European Journal of Immunology·Hansgeorg MüllerMartin Tiefenthaler
Feb 25, 2005·Transplantation·Torsten BöhlerJohannes Waiser
Apr 2, 2005·Biological & Pharmaceutical Bulletin·Takeyuki KohnoMasatoshi Hayashi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bradyarrhythmias

Bradyarrhythmias are slow heart rates. Symptoms may include syncope, dizziness, fatigure, shortness of breath, and chest pains. Find the latest research on bradyarrhythmias here.