Pharmacodynamics and pharmacokinetics of haloperidol and reduced haloperidol in guinea pigs.

Striatal homovanillic acid (HVA) levels and drug concentrations in striatum and plasma were examined in guinea pigs after acute and subchronic administrations of haloperidol (HAL) and reduced HAL (RHAL). HVA and drug levels were measured by high performance liquid chromatography with electrochemical detection. HAL and RHAL were interconverted in 10 min. Both maximal HVA responses and peak levels of HAL and RHAL in the striatum were reached at 2 h after injections of both HAL and RHAL. The potency of RHAL in HVA elevation was about one-half that of HAL, consistent with the HAL levels after RHAL and HAL administration. The higher the dose of HAL or RHAL injected, or after repeated injections, the greater the RHAL to HAL ratio produced. In addition, the RHAL to HAL ratios after RHAL were higher than those after HAL. These results suggest that the oxidative drug metabolizing systems are weaker than the reductive processes.