Abstract
The hydroxylation of the new antipsychotic drug risperidone to its main, active metabolite 9-hydroxyrisperidone is catalyzed by the hepatic cytochrome P450 enzyme CYP2D6, and cosegregates with the polymorphic hydroxylation of debrisoquin. We have previously examined central D2 dopamine and 5-HT2 receptor occupancy after 1 mg risperidone orally in three healthy subjects who were extensive metabolizers (EM) of debrisoquin, using positron emission tomography and the radioligands [11C]raclopride and [11C]NMSP. In this study, the same experimental design was repeated in two healthy poor metabolizers (PM) of debrisoquin to compare the D2 and 5-HT2 receptor occupancy induced by risperidone in EM and PM. The two PM had much higher plasma concentrations and longer elimination half-lives of risperidone than the three EM. Plasma concentrations of the sum of risperidone and 9-hydroxyrisperidone partly overlapped among the EM and PM. D2 receptor occupancy was 50% and 54% in the two PM, as compared to 40%, 43% and 55% in the EM. 5-HT2 receptor occupancy was 63% and 73%, as compared to 45%, 56% and 68% in the EM. These findings support the view that the active 9-hydroxyl metabolite of risperidone contributes to the in vivo effects of risperid...Continue Reading
References
Jan 1, 1992·Clinical Pharmacology and Therapeutics·M L DahlF Sjöqvist
Jan 1, 1991·International Journal of Radiation Applications and Instrumentation. Part B, Nuclear Medicine and Biology·C HalldinO Solin
Sep 1, 1990·Lancet·M Heim, U A Meyer
Jan 1, 1990·European Journal of Clinical Pharmacology·G AlvánU Gundert-Remy
Oct 1, 1989·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·L FardeC Halldin
May 1, 1989·The British Journal of Psychiatry : the Journal of Mental Science·T R Barnes
May 1, 1989·Clinical Pharmacology and Therapeutics·E J SanzL Bertilsson
Jan 1, 1986·International Journal of Radiation Applications and Instrumentation. Part A, Applied Radiation and Isotopes·R F DannalsH N Wagner
Jan 1, 1988·Psychopharmacology·L FardeS Stone-Elander
Jan 1, 1970·Acta Psychiatrica Scandinavica. Supplementum·G M Simpson, J W Angus
Jun 1, 1994·The American Journal of Psychiatry·S R Marder, R C Meibach
Jan 1, 1993·Psychopharmacology·S NybergB Eriksson
Feb 1, 1994·Psychopharmacology·L E van BeijsterveldtJ J Heykants
Jul 1, 1995·Synapse·L FardeC Halldin
Sep 1, 1993·Clinical Pharmacology and Therapeutics·M L HuangJ H Jonkman
Citations
Aug 7, 2003·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sandra BrunelleschiEugenio Torre
Feb 24, 2006·Acta Pharmacologica Sinica·Zhi-ling ZhouHuan-de Li
Jun 8, 2000·Clinical Pharmacokinetics·S Caccia
Jun 27, 2002·Clinical Pharmacokinetics·Marja-Liisa Dahl
Oct 13, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
Nov 12, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
Sep 2, 2011·Journal of Clinical Psychopharmacology·Dharmendra KumarAnita Kablinger
Jun 12, 2009·Drug Metabolism Reviews·Shu-Feng ZhouBalram Chowbay
Jul 4, 2012·Forensic Science International : Synergy·Eva SaarOlaf H Drummer
May 11, 2012·Drug Testing and Analysis·Eva SaarOlaf H Drummer
Dec 25, 2004·Drug Metabolism and Pharmacokinetics·Takako ShimizuNaoki Ozawa
Jul 2, 2004·Therapeutic Drug Monitoring·Christoph HiemkeMatthias J Müller
Jun 2, 2010·Pharmaceutics·David HolthoewerUlrich Schmitt
Nov 26, 2003·Therapeutic Drug Monitoring·Manickam AravagiriMichael J Gitlin
Mar 24, 2004·Molecular Psychiatry·J KirchheinerJ Brockmöller
Apr 24, 2007·Bone Marrow Transplantation·R E KastE L Altschuler
Jan 17, 2007·Journal of Clinical Psychopharmacology·Pieter W TroostPieter J Hoekstra
Sep 4, 2010·Journal of Clinical Psychopharmacology·Jesús NovalbosFrancisco Abad-Santos
Mar 1, 1996·Psychopharmacology·F P BymasterR W Fuller
Mar 1, 1996·Psychopharmacology·M E Stockton, K Rasmussen
Sep 16, 2017·CNS Spectrums·Abhinav AnandNavneet Khurana
Jan 1, 1997·Journal of Psychopharmacology·S Nyberg, L Farde
Sep 14, 2006·Pharmacological Reviews·Sharon J Gardiner, Evan J Begg
Aug 1, 2007·Personalized Medicine·Catarina Correia, Astrid M Vicente
Feb 20, 2021·Scientific Reports·Yaowaluck HongkaewChonlaphat Sukasem