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Pharmacokinetic study of metopimazine by oral route in children.

Mallet E, Bounoure F, Skiba M, Saussereau E, Goullé JP, Castanet M - Pharmacol Res Perspect (2015)

Bottom Line: MPZ was administered by oral route to 8 children with a single dose of 0.33 mg/kg during an endocrine exploration using stimuli well known for its adverse emetic effects.The plasmatic concentrations of AMPZ were higher than MPZ with a median C max of 76.3 ng/mL, a T max to 150 min and its concentration was approximately maintained at 50 ng/mL from 1 to 4 h.The plasmatic concentrations in children are similar to those observed in adults.

View Article: PubMed Central - PubMed

Affiliation: CIC INSERM 204, Department of Pediatrics, Rouen University Hospital Charles Nicolle, 76031, Rouen, France.

ABSTRACT
Metopimazine (MPZ) is an antiemetic considered as a currently used drug. In France, it has become the leading antiemetic mediator due to its good tolerance, however, its pharmacokinetics has never previously been studied in children. MPZ was administered by oral route to 8 children with a single dose of 0.33 mg/kg during an endocrine exploration using stimuli well known for its adverse emetic effects. We used biological remnants from sera following an hGH test in order to obtain the MPZ pharmacokinetics. Plasmatic concentrations of MPZ and the active acid metabolite AMPZ, were quantified by HPLC-MS/MS during a 270 min test period. MPZ is quickly absorbed with a median C max of 17.2 ng/mL at one hour and its half-life is 2.18 h. The plasmatic concentrations of AMPZ were higher than MPZ with a median C max of 76.3 ng/mL, a T max to 150 min and its concentration was approximately maintained at 50 ng/mL from 1 to 4 h. The plasmatic concentrations in children are similar to those observed in adults. No adverse effects, nausea or vomiting occurred during the trial. Therefore, these results confirm the MPZ dosage that should be used in children under 15 kg administered as 0.33 mg/kg up to 3 times a day.

No MeSH data available.


Related in: MedlinePlus

Mean plasmatic concentration of metopimazine (MPZ) and acid of MPZ in children (n = 8).
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fig03: Mean plasmatic concentration of metopimazine (MPZ) and acid of MPZ in children (n = 8).

Mentions: Due to AMPZ pharmacokinetics a single or double dose per day by oral route is possible in adults. Herrsted et al. showed that after a MPZ administration of 40 mg in six healthy volunteers, the median AMPZ Cmax of 296 ng/mL was obtained after a Tmax of 120 min. The mean concentration of AMPZ was always close to 70 ng/mL after 8 h. Moreover, after 8 h, the mean MPZ concentration was not detectable according to the MPZ half-life -time, that is, 2.18 h in this study. Therefore, the extended antiemetic activity was due to the AMPZ. The AMPZ half-life time could not be determined due to the insufficient amount of time available for the study. However, nevertheless AMPZ appears to have a greater half-life -time compared to MPZ and produced by MPZ deamination The AMPZ concentration appeared to be stable during the initial four hours of the trial. In Figure3, the mean AMPZ concentration was maintained at approximately 50 ng/mL from 1 to 4 h of the study time. AMPZ may also explain the good tolerance of MPZ. Also, MPZ has the lowest brain penetration of any antiemetic drug as compared to domperidone or metoclopramide. Jolliet et al. (2007) assessed the endothelial permeability of MPZ and AMPZ and showed that AMPZ has an endothelial permeability of 0.49 × 10−3 cm min−1 compared to 9.35 × 10−3 cm min−1 for MPZ, 44.9 × 10−3 cm min−1 for domperidone.


Pharmacokinetic study of metopimazine by oral route in children.

Mallet E, Bounoure F, Skiba M, Saussereau E, Goullé JP, Castanet M - Pharmacol Res Perspect (2015)

Mean plasmatic concentration of metopimazine (MPZ) and acid of MPZ in children (n = 8).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492748&req=5

fig03: Mean plasmatic concentration of metopimazine (MPZ) and acid of MPZ in children (n = 8).
Mentions: Due to AMPZ pharmacokinetics a single or double dose per day by oral route is possible in adults. Herrsted et al. showed that after a MPZ administration of 40 mg in six healthy volunteers, the median AMPZ Cmax of 296 ng/mL was obtained after a Tmax of 120 min. The mean concentration of AMPZ was always close to 70 ng/mL after 8 h. Moreover, after 8 h, the mean MPZ concentration was not detectable according to the MPZ half-life -time, that is, 2.18 h in this study. Therefore, the extended antiemetic activity was due to the AMPZ. The AMPZ half-life time could not be determined due to the insufficient amount of time available for the study. However, nevertheless AMPZ appears to have a greater half-life -time compared to MPZ and produced by MPZ deamination The AMPZ concentration appeared to be stable during the initial four hours of the trial. In Figure3, the mean AMPZ concentration was maintained at approximately 50 ng/mL from 1 to 4 h of the study time. AMPZ may also explain the good tolerance of MPZ. Also, MPZ has the lowest brain penetration of any antiemetic drug as compared to domperidone or metoclopramide. Jolliet et al. (2007) assessed the endothelial permeability of MPZ and AMPZ and showed that AMPZ has an endothelial permeability of 0.49 × 10−3 cm min−1 compared to 9.35 × 10−3 cm min−1 for MPZ, 44.9 × 10−3 cm min−1 for domperidone.

Bottom Line: MPZ was administered by oral route to 8 children with a single dose of 0.33 mg/kg during an endocrine exploration using stimuli well known for its adverse emetic effects.The plasmatic concentrations of AMPZ were higher than MPZ with a median C max of 76.3 ng/mL, a T max to 150 min and its concentration was approximately maintained at 50 ng/mL from 1 to 4 h.The plasmatic concentrations in children are similar to those observed in adults.

View Article: PubMed Central - PubMed

Affiliation: CIC INSERM 204, Department of Pediatrics, Rouen University Hospital Charles Nicolle, 76031, Rouen, France.

ABSTRACT
Metopimazine (MPZ) is an antiemetic considered as a currently used drug. In France, it has become the leading antiemetic mediator due to its good tolerance, however, its pharmacokinetics has never previously been studied in children. MPZ was administered by oral route to 8 children with a single dose of 0.33 mg/kg during an endocrine exploration using stimuli well known for its adverse emetic effects. We used biological remnants from sera following an hGH test in order to obtain the MPZ pharmacokinetics. Plasmatic concentrations of MPZ and the active acid metabolite AMPZ, were quantified by HPLC-MS/MS during a 270 min test period. MPZ is quickly absorbed with a median C max of 17.2 ng/mL at one hour and its half-life is 2.18 h. The plasmatic concentrations of AMPZ were higher than MPZ with a median C max of 76.3 ng/mL, a T max to 150 min and its concentration was approximately maintained at 50 ng/mL from 1 to 4 h. The plasmatic concentrations in children are similar to those observed in adults. No adverse effects, nausea or vomiting occurred during the trial. Therefore, these results confirm the MPZ dosage that should be used in children under 15 kg administered as 0.33 mg/kg up to 3 times a day.

No MeSH data available.


Related in: MedlinePlus