TY - JOUR T1 - Effect of quinidine on the interconversion kinetics between haloperidol and reduced haloperidol in humans: implications for the involvement of cytochrome P450IID6. AU - Young,D, AU - Midha,K K, AU - Fossler,M J, AU - Hawes,E M, AU - Hubbard,J W, AU - McKay,G, AU - Korchinski,E D, PY - 1993/1/1/pubmed PY - 1993/1/1/medline PY - 1993/1/1/entrez SP - 433 EP - 8 JF - European journal of clinical pharmacology JO - Eur J Clin Pharmacol VL - 44 IS - 5 N2 - Haloperidol (HAL) is a potent butyrophenone antipsychotic agent which is reversibly metabolized to reduced haloperidol (RHAL). In order to determine if this reversible metabolic pathway is linked to the debrisoquine 4-hydroxylase isozyme of cytochrome P-450 (P450IID6). HAL (5 mg) or RHAL (5 mg) was orally administered to healthy male volunteers in a randomized crossover design both with and without a prior (1 h) oral dose of quinidine (250 mg bisulfate), a potent inhibitor of this isozyme. Thirteen volunteers, 11 extensive metabolizers, 2 poor metabolizers, completed all four phases of the study. Plasma samples harvested over seven days were analysed for HAL and RHAL. An expression for the apparent fractional availability of metabolite from the parent compound given (Fapppm) was derived and was used to determine whether HAL or RHAL is the preferred metabolite, and whether quinidine co-administration alters Fapp for either compound. The AUC (0-t) for both HAL and RHAL were significantly greater following the administration of either compound with quinidine compared with AUC (0-t) values obtained in the absence of quinidine. The maximum plasma concentration (Cmax) of the administered compound was also greater following the administration of quinidine. Quinidine had no effect on the half-lives of the administered compounds. The Fapp for HAL and RHAL were not significantly affected by the administration of quinidine, indicating that the interconversion of HAL and RHAl is not linked to P450IID6. The Fapp of RHAL after administration of HAL was significantly greater than the Fapp of HAL after RHAL administration, indicating that RHAL is the preferred metabolic form. This difference was not affected by quinidine.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0031-6970 UR - https://www.unboundmedicine.com/medline/citation/8359179/Effect_of_quinidine_on_the_interconversion_kinetics_between_haloperidol_and_reduced_haloperidol_in_humans:_implications_for_the_involvement_of_cytochrome_P450IID6_ L2 - https://dx.doi.org/10.1007/BF00315539 DB - PRIME DP - Unbound Medicine ER -