The pharmacokinetics of intravenous and oral sulpiride in healthy human subjects

Abstract

The pharmacokinetics of sulpiride was studied in 6 healthy volunteers after intravenous and oral (tablets) administration of 100 mg. An open two- and in two subjects a three-compartment model was applied following intravenous administration. The average total distribution volume during the terminal slope was 2.72 +/- 0.66 l/kg and total systemic clearance was 415 +/- 84 ml/min. The serum half-life of the terminal slope following intravenous administration averaged 5.3 h (range 3.7--7.1 h) according to the two-compartment model. In two subjects the half-lives were 11.0 and 13.9 h when the three-compartment model was applied. Determinations of urinary excretion rates of unchanged sulpiride indicated a half-life of 7.15 h. Following intravenous administration, 70 +/- 9% of the dose was recovered unchanged in urine within 36 h; the mean renal clearance was 310 +/- 91 ml/min. Sulpiride was absorbed slowly, with peak concentrations appearing between 3 and 6 h after oral administration. The recovery of unchanged drug in urine following oral administration was 15 +/- 5% of the dose, with a mean renal clearance of 223 +/- 47 ml/min. The bioavailability determined from combined plasma and urine data was only 27 +/- 9%. The low bioavailability was probably due to incomplete absorption.

Pediatric Suppositories of Sulpiride Solid Dispersion for Treatment of Tourette Syndrome: In Vitro and In Vivo Investigations

“…The obtained results showed that the bioavailability after oral sulpiride SD administration was approximately 180% relative to the corresponding raw sulpiride suspension, an encouraging finding considering the reported 27-30% oral bioavailability after oral administration of sulpiride solution to humans (9,23). Tartaric acid as a hydrophilic carrier for SD development offers various advantages such as low toxicity, high compatibility, high water solubility, and low cost (24), which complied with the desired target product profile.…”

“…Following intravenous bolus dosing, sulpiride showed a distribution volume of 2.7 L/kg and a prolonged half-life of 11-14 h and was considered to be convenient for once-daily administration. Sulpiride showed slow and incomplete absorption from the gastrointestinal tract with a bioavailability not exceeding 27% (9). Moreover, it is worth noting that there are no rectal products of sulpiride in the market and scarce information exists on its rectal availability.…”

The Poorly Membrane Permeable Antipsychotic Drugs Amisulpride and Sulpiride Are Substrates of the Organic Cation Transporters from the SLC22 Family

“…The maximal plasma concentrations after oral administration of 50 mg amisulpride or 100 mg sulpiride are 0.13 and 0.29 μM, respectively (48,49). These values are much lower than the K M for the uptake of amisulpride and sulpiride by the transporters studied ( Table I), meaning that transport in vivo will not be saturated.…”

No Inhibition of Cytochrome P450 Activities in Human Liver Microsomes by Sulpiride, an Antipsychotic Drug

“…6,7) After oral administration of 100-400 mg in humans, peak plasma levels of 0.2-1.5 mg/ml are obtained within 1-3 h, and the elimination half life is 7-8 h. [8][9][10] After intravenous administration of sulpiride, 70% of the dose is recovered as unchanged drug in urine, as compared to 15% after oral administration, 11) and the bioavailability of the oral form is 25-36%. 10,11) After oral dosing of 14 C-labeled sulpiride, urinary excretion of radioactivity was 27-52%, and more than 95% of the radioactivity recovered in the urine and feces is unchanged sulpiride. 8) It has been reported that sulpiride is coadministered with other drugs including olanzapine, 12,13) fluvoxamine, 14) and cimetidine 15) for the treatment of schizophrenia, depression, and gastro-duodenal ulcers, respectively.…”