Tolerability and Pharmacokinetic Comparison of Oral, Intramuscular, and Intravenous Administration of Levosulpiride After Single and Multiple Dosing in Healthy Chinese Volunteers

Xu, Mingzhen; Zhou, Ying; Ni, Yang; He, Xiaomeng; Li, Huqun; Sattar, Harse; Chen, Hui; Li, Weiyong

doi:10.1016/j.clinthera.2015.08.024

Cited by 14 publications

(10 citation statements)

References 12 publications

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“…The V ss of LSP in the current study was small, in agreement with those reported for sulpiride in the donkey and horse (Giorgi et al, , ). The V ss for LSP calculated in pharmacokinetic study in humans after IV administration (Xu et al, ) is higher than that in the present study but still moderate (1,300 ml/kg). IM and IV administrations resulted in similar half‐lives (1.36 ± 0.06 vs. 1.38 ± 0.17 hr), a finding in‐line with those reported after IV and IM LSP in humans (Xu et al, ) and sulpiride administration in the horse, donkey, and (Giorgi et al, , ) humans (Brès & Bressolle, ; Wiesel, Alfredsson, Ehrnebo, & Sedvall, ).…”

Section: Discussioncontrasting

confidence: 78%

“…The different vascularization of the injection site (neck vs. gluteal muscle) between these studies might explain the difference in reported F %. The IM F % of LSP in humans was higher than that reported in this study (96.8% Xu et al, ).…”

Section: Discussioncontrasting

confidence: 75%

“…After oral administration, LSP plasma concentrations were erratic. The oral F % of LSP and sulpiride is low in humans: 23.4%; (Xu et al, ) and 35% (Bressolle, Brès, & Fauré‐Jeantis, ), respectively and in animals as horses (20.4%; Giorgi et al, ), and donkeys (9.4%; Giorgi et al, ). In the current study was even lower 4.73%.…”

Section: Discussionmentioning

confidence: 99%

“…LSP after oral administration is rapidly adsorbed from the gastrointestinal tract in humans. It has a T max of around 3 hr and a half‐life of 12 hr (Xu et al, ). The main elimination route is via the kidney (Rossi & Forgione, ).…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of levosulpiride after single‐dose administration in goats (Capra hircus) by different routes of administration

Łebkowska‐Wieruszewska

Barsotti

Camillo

et al. 2019

Vet Pharm & Therapeutics

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Levosulpiride (LSP) is the l‐enantiomer of sulpiride, and LSP recently replacing sulpiride in several EU countries. Several studies about LSP in humans are present in the literature, but neither pharmacodynamic nor pharmacokinetic data of LSP is present for veterinary species. The aim of this study was to assess the pharmacokinetic profile of LSP after intravenous (IV), intramuscular (IM), and oral (PO) administration in goats. Animals (n = 6) were treated with 50 mg LSP by IV, IM, and PO routes according to a randomized cross‐over design (3 × 3 Latin‐square). Blood samples were collected prior and up to 24 hr after LSP administration and quantified using a validated HPLC method with fluorescence detection. IV and IM administration gave similar concentration versus time curve profiles. The IM mean bioavailability was 66.97%. After PO administration, the drug plasma concentrations were detectable only in the time range 1.5–4 hr, and the bioavailability (4.73%) was low. When the AUC was related to the administered dose in mg/kg, there was a good correlation in the IV and IM groups, but very low correlation for the PO route. In conclusion, the IM and IV administrations result in very similar plasma concentrations. Oral dosing of LSP in goats is probably not viable as its oral bioavailability was very low.

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Section: Discussioncontrasting

confidence: 78%

Section: Discussioncontrasting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacokinetics of levosulpiride after single‐dose administration in goats (Capra hircus) by different routes of administration

Łebkowska‐Wieruszewska

Barsotti

Camillo

et al. 2019

Vet Pharm & Therapeutics

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“…OCTN2 dysfunction would potentially result in diseases such as heart failure, muscle weakness and hypoglycemia (Grube et al, ; Shekhawat et al, ). The maximum plasma or tissue concentrations of sulpiride in human are about 0.5 μ m after a single oral administration of sulpiride at a dose of 100 mg/day (Wiesel et al, ; Xu et al, ; Zhao, Liao, & Yang, ) and a high accumulation of the sulpiride was observed in the kidney after oral administration of sulpiride (500 mg) (Takano et al, ). The evaluated IC 50 values of sulpiride for OCTN2 ( l ‐carnitine for substrate) and OCTN1 (ergothioneine for substrate) were approximately 30 μ m and 100 μ m , respectively.…”

Section: Discussionmentioning

confidence: 99%

Multiple organic cation transporters contribute to the renal transport of sulpiride

Weng

Wang

et al. 2017

Biopharm & Drug Disp

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Sulpiride, a selective dopamine D2 receptor blocker, is used widely for the treatment of schizophrenia, depression and gastric/duodenal ulcers. Because the great majority of sulpiride is positively charged at physiological pH 7.4, and ~70% of the dose recovered in urine is in the unchanged form after human intravenous administration of sulpiride, it is believed that transporters play an important role in the renal excretion of sulpiride. The aim of the present study was to explore which transporters contribute to the renal disposition of sulpiride. The results demonstrated that sulpiride was a substrate of human carnitine/organic cation transporter 1 (hOCTN1) and 2 (hOCTN2), human organic cation transporter 2 (hOCT2), human multidrug and toxin efflux extrusion protein 1 (hMATE1) and 2-K (hMATE2-K). Sulpiride accumulation from the basolateral (BL) to the apical (AP) side in MDCK-hOCT2/pcDNA3.1 cell monolayers was much greater than that in MDCK-hOCT2/hMATE1 cells, and cimetidine dramatically reduced the intracellular accumulation of sulpiride from BL to AP. In addition, the accumulation of sulpiride in mouse primary renal tubular cells (mPRTCs) was markedly reduced by inhibitors of Oct2 and Octns. The results implied that OCTN1, OCTN2, OCT2, MATE1 and MATE2-K probably contributed to the renal transfer of sulpiride, in which OCT2 mediated the uptake of sulpiride from the bloodstream to the proximal tubular cells, while MATEs contributed to the sulpiride efflux from the proximal tubular cells to the renal lumen, and OCTNs participated in both renal secretion and reabsorption.

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Pharmacokinetics and Pharmacodynamics of Gastrointestinal Drugs

Yoon

2022

Sex/Gender-Specific Medicine in the Gastrointestinal Diseases

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Tolerability and Pharmacokinetic Comparison of Oral, Intramuscular, and Intravenous Administration of Levosulpiride After Single and Multiple Dosing in Healthy Chinese Volunteers

Cited by 14 publications

References 12 publications

Pharmacokinetics of levosulpiride after single‐dose administration in goats (Capra hircus) by different routes of administration

Pharmacokinetics of levosulpiride after single‐dose administration in goats (Capra hircus) by different routes of administration

Multiple organic cation transporters contribute to the renal transport of sulpiride

Pharmacokinetics and Pharmacodynamics of Gastrointestinal Drugs

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