Pharmacokinetic-pharmacodynamic study of oral lansoprazole 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.