PMID- 18035206
OWN - NLM
STAT- MEDLINE
DCOM- 20080108
LR  - 20131121
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 29
IP  - 9
DP  - 2007 Sep
TI  - Pharmacokinetics and tolerability of rabeprazole sodium in subjects aged 12 to 16 
      years with gastroesophageal reflux disease: an open-label, single- and 
      multiple-dose study.
PG  - 2082-92
AB  - OBJECTIVE: This study was conducted to characterize the pharmacokinetic and 
      safety profile of rabeprazole sodium tablets in children and adolescents with 
      gastroesophageal reflux disease (GERD). METHODS: This was a multicenter, 
      open-label, single- and multiple-dose study in subjects aged 12 to 16 years with 
      GERD. Subjects were stratified by age (12-<14 years and 14-16 years) and were 
      randomized to receive oral rabeprazole 10 or 20 mg/d over 5 or 7 days (to 
      accommodate weekends). The pharmacokinetic parameters calculated included C(max), 
      T(max), AUC, t(1/2), and apparent oral clearance (day 5/7 only). Blood samples 
      for pharmacokinetic determinations were obtained on study days 1, 2, and 5 (or 7) 
      and at discharge on day 6 (or 8). Safety assessments, including adverse events 
      (AEs), were performed at all study visits. RESULTS: Twenty-four subjects were 
      enrolled in the study (12 in each dose group); they were predominantly white, had 
      a mean age of 14.2 years, and had a mean body mass index of 24.3 kg/m(2) (the 
      90th percentile for adolescents of this age in the United States). Mean age and 
      weight did not differ significantly between the 2 dose groups. On day 1, C(max) 
      was significantly greater in the rabeprazole 20-mg group compared with the 
      rabeprazole 10-mg group (P = 0.024); on day 5/7, both AUC and C(max) were 
      significantly greater in the rabeprazole 20-mg group compared with the 
      rabeprazole 10-mg group (P = 0.005 and P = 0.007, respectively). Within-period 
      comparisons for both groups indicated that the AUC and C(max) for rabeprazole and 
      its thioether metabolite did not differ significantly from day 1 to day 5/7. In 
      addition, the T(max) and t(1/2) were relatively unchanged from day 1 to day 5/7 
      in both dose groups. Treatment-emergent signs and symptoms occurred in 11 
      subjects, 6 in the 10-mg group and 5 in the 20-mg group. The most frequently 
      reported AEs were headache and nausea (16.7% and 8.3%, respectively). No 
      statistically significant differences were observed between dose groups in terms 
      of the number of subjects with AEs. CONCLUSIONS: Rabeprazole 10 and 20 mg were 
      well tolerated in these children and adolescents with GERD. The results of the 
      pharmacokinetic analyses of single and multiple oral doses indicated no apparent 
      accumulation of rabeprazole or its thioether metabolite with the 10-mg dose. 
      There was, however, a suggestion of accumulation with multiple dosing of 
      rabeprazole 20 mg, which requires confirmation in larger studies.
FAU - James, Laura
AU  - James L
AD  - Department of Pediatrics, University of Arkansas for Medical Sciences, Little 
      Rock, Arkansas, USA. jameslaurap@uams.edu
FAU - Walson, Philip
AU  - Walson P
FAU - Lomax, Kathleen
AU  - Lomax K
FAU - Kao, Richard
AU  - Kao R
FAU - Varughese, Shanti
AU  - Varughese S
FAU - Reyes, Josephine
AU  - Reyes J
CN  - Study 119 Pediatric Trial Investigators
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (2-Pyridinylmethylsulfinylbenzimidazoles)
RN  - 0 (Anti-Ulcer Agents)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0 (Tablets)
RN  - 32828355LL (Rabeprazole)
SB  - IM
MH  - *2-Pyridinylmethylsulfinylbenzimidazoles/administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Adolescent
MH  - Analysis of Variance
MH  - *Anti-Ulcer Agents/administration & dosage/adverse effects/pharmacokinetics
MH  - Area Under Curve
MH  - Child
MH  - Drug Administration Schedule
MH  - Female
MH  - Gastroesophageal Reflux/*drug therapy
MH  - Humans
MH  - Male
MH  - *Proton Pump Inhibitors/administration & dosage/adverse effects/pharmacokinetics
MH  - Rabeprazole
MH  - Tablets
EDAT- 2007/11/24 09:00
MHDA- 2008/01/09 09:00
CRDT- 2007/11/24 09:00
PHST- 2007/06/28 00:00 [accepted]
PHST- 2007/11/24 09:00 [pubmed]
PHST- 2008/01/09 09:00 [medline]
PHST- 2007/11/24 09:00 [entrez]
AID - S0149-2918(07)00288-3 [pii]
AID - 10.1016/j.clinthera.2007.09.007 [doi]
PST - ppublish
SO  - Clin Ther. 2007 Sep;29(9):2082-92. doi: 10.1016/j.clinthera.2007.09.007.