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Pharmacokinetic-pharmacodynamic study of oral lansoprazole in children
Agnès Tran1, Elisabeth Rey, Gérard Pons
1Pharmacologie Périnatale et Pédiatrique, Gastroentérologie Pédiatrique, Université René Descartes, Hôpital Saint-Vincent de Paul, 82 Avenue Denfert-Rochereau, Assistance Publique-Hôpitaux de Paris, 75674 Paris, France.
Insights
Lansoprazole is safe for children, with pharmacokinetics and antisecretory effects varying by age. Infants may eliminate the drug faster and show greater acid suppression than older children.
Area of Science:
- Pediatric pharmacology
- Gastroenterology
- Drug metabolism
Background:
- Proton pump inhibitors (PPIs) like lansoprazole are crucial for managing acid-related disorders in children.
- Understanding lansoprazole's behavior in pediatric populations is essential for optimizing treatment.
- Limited data exists on pediatric pharmacokinetics and pharmacodynamics of lansoprazole.
Purpose of the Study:
- To investigate the pharmacokinetics, pharmacodynamics, and tolerability of lansoprazole in children.
- To assess lansoprazole's antisecretory effects after single and multiple doses.
- To explore age-related differences in lansoprazole's drug behavior and efficacy.
Main Methods:
- Open-label study involving 40 children (18 days to 14 years) with gastric acid-related disorders.
- Administration of lansoprazole: single dose (17 mg/m²) or multiple doses (17 mg/m²/day) for 7-14 days.
- Measurement of lansoprazole plasma concentrations (HPLC) and 24-hour intragastric pH monitoring.
Main Results:
- Pharmacokinetic parameters (Cmax, Tmax, half-life, AUC, clearance, Vd) were determined for single and multiple doses.
- No significant age influence on pharmacokinetics, but reduced elimination in neonates and higher elimination in infants suggested.
- Antisecretory effect (gastric pH <4 and <3) decreased with age; correlated with Cmax and AUC in single-dose group.
- Mean gastrin serum concentration increased after multiple doses.
Conclusions:
- Lansoprazole demonstrated good tolerability in pediatric patients.
- Infants may exhibit faster elimination and greater antisecretory effects compared to older children and adults.
- Age-specific dosing or monitoring may be beneficial for optimizing lansoprazole therapy in children.
Objective:
We investigated the pharmacokinetics, pharmacodynamics, and tolerability of lansoprazole in children after single and multiple administrations.
Methods:
Forty children (age range, 18 days-14 years) with gastric acid-related disorders entered an open study and received lansoprazole in a single dose of 17 mg. m(-2) (group A) or in multiple doses (17 mg. m(-2) per day) for 7 to 14 days (group B). Lansoprazole plasma concentrations were measured by HPLC. A 24-hour intragastric pH monitoring assessed the antisecretory effect.
Results:
In group A, maximal concentration (C(max)) was 1023 +/- 775 (mg. L(-1))/(17 mg. m(-2)), time to reach C(max) was 1.8 +/- 0.8 hours, elimination half-life was 1.5 +/- 2.0 hours, area under the concentration-time curve from time zero to infinity [AUC(0-infinity)] was 3503 +/- 6025 (mg. L(-1). h)/(17 mg. m(-2)), apparent plasma clearance was 0.57 +/- 0.47 L. h(-1). kg(-1), and apparent volume of distribution was 0.61 +/- 0.36 L. kg(-1). In group B, C(max) was 750 +/- 511 (mg. L(-1))/(17 mg. m(-2)), time to reach C(max) was 1.8 +/- 1.1 hours, elimination half-life was 1.2 +/- 1.1 hours, AUC(0-infinity) was 2351 +/- 3691 (mg. L(-1). h)/(17 mg. m(-2)), apparent plasma clearance was 0.71 +/- 0.50 L. h(-1). kg(-1), and apparent volume of distribution was 0.9 +/- 0.7 L. kg(-1). No influence of age was shown on pharmacokinetic parameters in both groups. However, data suggested that elimination was reduced in neonates and higher in infants than in adults. The values for 24-hour percentage of time at gastric pH <4 and pH <3 were 61% +/- 21% and 51% +/- 21% (group A) and 47% +/- 24% and 37% +/- 21% (group B), respectively. In both groups the antisecretory effect decreased with age, and in group A it was positively correlated to C(max) and AUC(0-infinity). The mean gastrin serum concentration significantly increased (+31%) after 12.6 +/- 1.5 days of treatment.
Conclusions:
Lansoprazole was well tolerated in children. After a single oral dose of 30 mg per 1.73 m(2), there was a trend for the elimination to be higher in infants than in adults and the antisecretory effect appeared to be higher in infants younger than 6 months than in older children and adults.