Prolactin Responsiveness to Repeated Decremental Doses of Sulpiride

Abstract

The variation in the prolactin response to sulpiride was studied in six normal men by repeating the same dose of the drug (50 mg) after 24 hours and on three subsequent occasions, repeating this 2 day test at an interval of 6 days with progressively halved doses of sulpiride. A similar PRL response occurred on the first day of each test period and the peak response was highly significant (P less than 0.001), occurring within 30 minutes. A gross blunting of the PRL response on the second day of each period was noted throughout the study. The difference in delta PRL between the first and second day of each period was highly significant (P less than 0.001). The delta PRL increment on the second day was inversely proportional to the dose of sulpiride; the differences in delta PRL between periods 1 and 3 and periods 1 and 4 being highly significant (P less than 0.001). This study suggests that a much lower dose of sulpiride than that normally used is adequate to stimulate PRL secretion and that care must be taken in the timing of repeat testing.

Prolactin response to low dose sulpiride.

“…1I I I IV T I Although there were no differences in area under the curve, the prolactin response to 1 mg sulpiride after 7 days dosing was only 50% (peak levels) of that seen on the first day of exposure to the drug. This attenuation of response after chronic treatment complements the observations of Tormey et al (1981) and Cohen et al (1983) who demonstrated a refractory period in the response of prolactin to sulpiride at 2, 8 and 24 h after dosage. The reason for this is not clear, but it is possible that dopamine turnover increases in response to blockade, as has been demonstrated in the rat (Annunziato etal., 1980) such that with chronic therapy, an increased amount of drug is required to produce the same effect.…”

Influence of the dosing interval on prolactin release after remoxipride.

“…The peak plasma prolactin levels (Cmax,PRL) have been reported to be dose-related up to a maximal release following administration of remoxipride [13,14,29], sulpiride [16,[21][22][23][24][25] and also following TRH [26,27]. Maximal prolactin peak concentrations are expected to be achieved with the doses of remoxipride and TRH administered in the present study [26,27].…”

“…Findings during repeated administration of remoxipride to patients, where the prolactin response with regard to peak plasma prolactin concentrations diminished, led us to be interested in prolactin responsiveness in relation to dosing intervals [12][13][14]. Results on prolactin release from the literature regarding administration of other neuroleptics (sulpiride, haloperidol) and TRH have suggested a refractory period of prolactin response [15][16][17]. The refractory period was seen as lack of prolactin increase or a grossly blunted increase after a 24 h dosing interval of sulpiride in man [15,16].…”

“…Results on prolactin release from the literature regarding administration of other neuroleptics (sulpiride, haloperidol) and TRH have suggested a refractory period of prolactin response [15][16][17]. The refractory period was seen as lack of prolactin increase or a grossly blunted increase after a 24 h dosing interval of sulpiride in man [15,16].…”