Single‐Dose Pharmacokinetics of Nizatidine (Axid®) in Children

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 postdose blood samples taken over a 12‐hour period. The apparent terminal elimination rate constant for nizatidine in the pediatric subjects (0.58 +− 0.8 h −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., C max' CL/F, V ss /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., AUC 0–∞ ) 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 EC 50 value of the drug for gastric acid suppression determined from adult studies for approximately 6 hours.