PMID- 21740077
OWN - NLM
STAT- MEDLINE
DCOM- 20111027
LR  - 20211020
IS  - 1179-1926 (Electronic)
IS  - 0312-5963 (Linking)
VI  - 50
IP  - 8
DP  - 2011 Aug
TI  - Randomized, open-label, multicentre pharmacokinetic studies of two dose levels of 
      pantoprazole granules in infants and children aged 1 month through <6 years with 
      gastro-oesophageal reflux disease.
PG  - 541-50
LID - 10.2165/11591900-000000000-00000 [doi]
AB  - BACKGROUND AND OBJECTIVE: The primary objective of this study was to characterize 
      the pharmacokinetic profile of pantoprazole delayed-release granules in infants 
      and children aged 1 month to <6 years with gastro-oesophageal reflux disease 
      (GORD). The studies described in this manuscript were conducted to fulfil the 
      requirements of the paediatric written request for pantoprazole by the US FDA. 
      METHODS: Two randomized, open-label, multicentre studies were conducted in 
      infants aged 1 month to <12 months (study 1) and children aged 1 year through <6 
      years (study 2) with GORD. Patients were randomly assigned to either the low-dose 
      pantoprazole group (0.6 mg/kg equivalent) or the high-dose pantoprazole group 
      (1.2 mg/kg equivalent) in a 1 : 1 fashion. Pantoprazole granules were 
      administered approximately 30 minutes before breakfast for at least five 
      consecutive doses. Blood samples were obtained at prespecified intervals. Plasma 
      pantoprazole concentration-time data were analysed by non-compartmental methods. 
      Descriptive statistics were calculated for pharmacokinetic parameters. Patients 
      in study 2 additionally received pantoprazole for 28 days. Safety was monitored 
      throughout. RESULTS: In study 1, 43 patients were randomized; 42 were included in 
      the single-dose pharmacokinetic evaluation (15 females, 27 males; mean postnatal 
      age 6.3 months). In study 2, 17 patients were randomized, and all were included 
      in the single-dose pharmacokinetic evaluation (6 females, 11 males; mean age 3.2 
      years). In both studies, exposure increased with dose. Mean (standard deviation) 
      maximum (peak) plasma concentration values for the low and high doses were 503 
      (506) ng/mL and 1318 (1307) ng/mL, respectively, in study 1, and 229 (196) ng/mL 
      and 653 (645) ng/mL, respectively, in study 2. Area under the plasma 
      concentration-time curve values for the low and high doses were 1046 (1043) ng . 
      h/mL and 3602 (3269) ng . h/mL, respectively, in study 1, and 293 (146) ng . h/mL 
      and 2448 (2170) ng . h/mL, respectively, in study 2. There was a trend for 
      increasing clearance with increasing age across the ages 1 month through <6 
      years. There was no evidence of drug accumulation after multiple doses. 
      On-treatment adverse events (AEs) occurred in 19 of 43 patients in study 1 and in 
      11 of 17 patients in study 2. Serious AEs occurred in two patients in study 1 
      (gastroenteritis in one patient and acute gastroenteritis from rotavirus 
      infection resulting in discontinuation of one patient); the serious AEs resolved 
      and were not considered by the investigators to be drug related. No other 
      safety-related discontinuations occurred in either study. CONCLUSIONS: Exposure 
      increased with increasing doses of pantoprazole granules, even though wide 
      interindividual variability was observed. Compared with that in adults receiving 
      pantoprazole 40 mg, exposure obtained with the 1.2 mg/kg dose was similar in 
      study 1 and slightly lower in study 2. Pantoprazole was generally well tolerated 
      in infants and children aged 1 month through <6 years with GORD. Trial 
      registration numbers (ClinicalTrials.gov): NCT00259012 (study 1) and NCT00141817 
      (study 2).
FAU - Tammara, Brinda K
AU  - Tammara BK
AD  - Pfizer Inc., Collegeville, PA 19426, USA. brinda.tammara@pfizer.com
FAU - Sullivan, Janice E
AU  - Sullivan JE
FAU - Adcock, Kim G
AU  - Adcock KG
FAU - Kierkus, Jaroslaw
AU  - Kierkus J
FAU - Giblin, John
AU  - Giblin J
FAU - Rath, Natalie
AU  - Rath N
FAU - Meng, Xu
AU  - Meng X
FAU - Maguire, Mary K
AU  - Maguire MK
FAU - Comer, Gail M
AU  - Comer GM
FAU - Ward, Robert M
AU  - Ward RM
LA  - eng
SI  - ClinicalTrials.gov/NCT00141817
SI  - ClinicalTrials.gov/NCT00259012
GR  - U10 HD045986/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Clin Pharmacokinet
JT  - Clinical pharmacokinetics
JID - 7606849
RN  - 0 (2-Pyridinylmethylsulfinylbenzimidazoles)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0 (Suspensions)
RN  - D8TST4O562 (Pantoprazole)
SB  - IM
MH  - 2-Pyridinylmethylsulfinylbenzimidazoles/administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Administration, Oral
MH  - Age Factors
MH  - Area Under Curve
MH  - Child, Preschool
MH  - Delayed-Action Preparations
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Gastroesophageal Reflux/*drug therapy
MH  - Humans
MH  - Infant
MH  - Male
MH  - Pantoprazole
MH  - Proton Pump Inhibitors/administration & dosage/adverse effects/*pharmacokinetics
MH  - Suspensions
EDAT- 2011/07/12 06:00
MHDA- 2011/10/28 06:00
CRDT- 2011/07/12 06:00
PHST- 2011/07/12 06:00 [entrez]
PHST- 2011/07/12 06:00 [pubmed]
PHST- 2011/10/28 06:00 [medline]
AID - 6 [pii]
AID - 10.2165/11591900-000000000-00000 [doi]
PST - ppublish
SO  - Clin Pharmacokinet. 2011 Aug;50(8):541-50. doi: 10.2165/11591900-000000000-00000.