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Single-dose pharmacokinetics of nizatidine (Axid) in children
Susan M Abdel-Rahman1, Franklin K Johnson, Neil Manowitz
1Division of Pediatric Clinical Pharmacology and Medical Toxicology, Children's Mercy Hospital and Clinics, Kansas City, Missouri 64108, USA.
Insights
This study found that nizatidine pharmacokinetics in children are similar to adults, with comparable drug levels and gastric acid suppression duration after a liquid dose. Nizatidine metabolism was approximately 15%.
Area of Science:
- Pediatric Pharmacology
- Drug Metabolism and Pharmacokinetics
Background:
- Nizatidine is a histamine H2 receptor antagonist used for gastric acid suppression.
- Limited pharmacokinetic data exists for nizatidine in pediatric populations, especially for liquid formulations.
Purpose of the Study:
- To evaluate the pharmacokinetics of nizatidine in healthy children following an oral liquid dose.
- To compare pediatric nizatidine pharmacokinetics with existing adult data.
Main Methods:
- 12 healthy children received a single 5.0 mg/kg oral dose of nizatidine in apple juice.
- Nizatidine and N-desmethylnizatidine plasma concentrations were measured using HPLC/MS over 12 hours.
- Pharmacokinetic parameters were calculated and compared to adult studies.
Main Results:
- The apparent terminal elimination rate constant in children was similar to adults (0.58 vs. 0.54 h⁻¹).
- Corrected for bioavailability, pediatric pharmacokinetic parameters (Cmax, CL/F, Vss/F) were comparable to adults receiving solid doses.
- Approximately 15% of nizatidine was metabolically converted to N-desmethylnizatidine.
- Plasma concentrations exceeded the effective concentration for gastric acid suppression for approximately 6 hours.
Conclusions:
- Nizatidine pharmacokinetics in children are similar to adults, supporting the use of similar dosing strategies.
- Liquid nizatidine formulations in children achieve comparable systemic exposure and duration of action to adult solid doses.
- The findings support the efficacy of nizatidine for gastric acid suppression in pediatric patients.
Abstract:
The pharmacokinetics of nizatidine following a single 5.0 mg/kg oral dose given as an extemporaneous liquid formulation in apple juice was examined in 12 healthy children (8.0 +/- 2.4 years, 30.7 +/- 8.4 kg). Nizatidine and N-desmethylnizatidine were quantitated by HPLC/MS from five post dose blood samples taken over a 12-hour period. The apparent terminal elimination rate constant for nizatidine in the pediatric subjects (0.58 +/- 0.8h(-1)) was virtually identical to that (0.54 +/- 0.13 h(-1)) previously reported from adult studies. When corrected for an estimated 30% reduction in nizatidine oral bioavailability observed in adults upon coingestion of the drug with other fruit/vegetable juices, nizatidine pharmacokinetic parameter estimates (e.g., Cmax, CL/F, Vss/F) in our pediatric subjects were similar to those previously reported in adults who were administered dimensionally similar (e.g., approximately 4 mg/kg) solid oral doses of the drug. Examination of the mean area under the curve (i.e., AUC0-infinity for nizatidine and N-desmethylnizatidine suggested an approximate 15% metabolic conversion of the parent drug. Finally, nizatidine plasma concentrations in pediatric patients following a single 5.0 mg/kg oral dose exceeded the EC50 value of the drug for gastric acid suppression determined from adult studies for approximately 6 hours.