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Plasma levels of benperidol, prolactin, and homovanillic acid after intravenous versus two different kinds of oral application of the neuroleptic in schizophrenic patients.

Plasma levels of prolactin (PRL) and the butyrophenone neuroleptic benperidol (BPD) were closely followed 0 to 48 h after acute application of 6 mg BPD as intravenous injection, orally as liquid, and orally as tablets in 12 schizophrenic patients using a partially randomized cross over design. Drug concentrations showed application specific pharmacokinetic behavior with complete elimination within 48 h. All three applications led to a biphasic PRL response with pronounced initial plasma PRL peaks returning to baseline levels within 48 h. The results suggest that after acute neuroleptic challenge BPD plasma levels as low as 2-3 ng/ml can be sufficient for complete depletion of pituitary PRL stores. This initial peak was followed by a PRL plateau about twice above pretreatment values indicating doubling of the PRL synthesis and secretion independent of supraeffective actual BPD concentrations. The PRL plateau persisted as long as BPD concentrations were above those levels which triggered the initial PRL response. As compared with the time of maximum concentrations (tmax) for BPD, the PRL tmax was later after i.v. injection, equal after liquid application, and earlier after tablet administration leading to pronounced application specific differences in shape, direction, and position of resulting hysteresis curves. Plasma levels of homovanillic acid (HVA) were not affected by BPD treatment. The PRL and HVA levels registered after acute doses of BPD indicated that the hormone responses were most likely the result of acute depletion of PRL stores and subsequent stimulation of hormone synthesis whereas it seemed unlikely that dopaminergic activities were relevant.