Summary
Sulpiride (SU), a widelyused benzamide neuroleptic, is known to promote rapid prolactin release. Sulpiride plasmalevel and the prolactin response to the most commonly used dose, i.e., 50 and 200 mg sulpiride (ad-ministered orally), were studied inten male volunteers.
The design of this study permitted the simultaneous measurement of the sulpiride plasma level for 48 hours, by means of a new HPLC-electrochemical detection method, and of the prolactin level, by means of RIA.
Pharmacokinetic study of sulpiride showed that the mean concentration and time of peak plasma level of the two doses were different: 77 ng/ml SU at 2.3h for the 50 mg dose and 243 ng/ml at 3.5 h for the 200 mg dose. The absorption and elimination rateconstants were similar regardless of the dose. (ka: 1.05–1.9 h−1; t1/2β: 25 h).. A linear relationship of the area underthe plasmatic concentration versus time curve with the dose was observed. Mean plasma leveldecreased for both doses to about 14%of peak value at48 hours.
Prolactin serum levels increased from the basal value after SU administration with marked individual differences. The 200 mg dose resulted in earlier prolactin peak levels (54 ng/ml between 30 min and 1 h) than the 50 mg dose (50 ng/ml between 1 and 2 h). The prolactin level then decreased and remained constant at about 15 ng/ml for 11 to 48 h. Prolactin levels returned to basal values (mean: 5 ng/ml) after one week.
It is concludedthat therapeutic doses of sulpiride induce prolactin secretion thatis dose-dependent in a first phase and stimulated independently of the sulpiride concentration in a second phase. A mechanism of indirect action mediated by PRL is suggested to explainthe neurolepticactivityofthe drug.
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Part of this work was presented at the 12th CINP Congress, 22–26 June 1980, Göteborg, Sweden.
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Sugnaux, F.R., Benakis, A., Fonzo, D. et al. Dose-dependent pharmacokinetics of sulpirideand sulpiride-induced prolactin secretionin man. European Journal of Drug Metabolism and Pharmacokinetics 8, 189–200 (1983). https://doi.org/10.1007/BF03188745
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DOI: https://doi.org/10.1007/BF03188745