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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.


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Plasmatic concentration of metopimazine in eight children.
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fig02: Plasmatic concentration of metopimazine in eight children.

Mentions: MPZ is metabolized by the liver into MPZ acid. This active metabolite appears at the same time as MPZ due to a first pass metabolism. AMPZ plasmatic concentrations for each child are represented in Figure2. The AMPZ plasmatic concentrations are higher than MPZ with a median Cmax of 73.6 ng/mL [range 36.9–145.7] and a Tmax to 150 min. The ratio of Cmax AMPZ/MPZ is 4.28. These results are in agreement with the study reported by Herrstedt et al. (1990). After a preprandial oral dose of 20 mg, these authors observed a Tmax of 120 min, a median Cmax of 107.5 ng/mL for AMPZ and a Cmax ratio of 1.72. They found a wide range between MPZ and AMPZ serum concentrations. Also, they were higher than the concentrations generally found due to the use of a higher dose rather than that recommended in the CTD. Also, the MPZ and AMPZ concentrations were higher. This result is in accordance with data published in the literature. Herrstedt et al. (1990) also reported a highly significant interindividual variation in MPZ AUC.


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)

Plasmatic concentration of metopimazine in eight children.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Plasmatic concentration of metopimazine in eight children.
Mentions: MPZ is metabolized by the liver into MPZ acid. This active metabolite appears at the same time as MPZ due to a first pass metabolism. AMPZ plasmatic concentrations for each child are represented in Figure2. The AMPZ plasmatic concentrations are higher than MPZ with a median Cmax of 73.6 ng/mL [range 36.9–145.7] and a Tmax to 150 min. The ratio of Cmax AMPZ/MPZ is 4.28. These results are in agreement with the study reported by Herrstedt et al. (1990). After a preprandial oral dose of 20 mg, these authors observed a Tmax of 120 min, a median Cmax of 107.5 ng/mL for AMPZ and a Cmax ratio of 1.72. They found a wide range between MPZ and AMPZ serum concentrations. Also, they were higher than the concentrations generally found due to the use of a higher dose rather than that recommended in the CTD. Also, the MPZ and AMPZ concentrations were higher. This result is in accordance with data published in the literature. Herrstedt et al. (1990) also reported a highly significant interindividual variation in MPZ AUC.

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