The bioequivalence of nizatidine (Axid) in two extemporaneously and one commercially prepared oral liquid formulations compared with capsule.
Nizatidine (Axid) is an H2-receptor antagonist used for the treatment of acid-related gastrointestinal disorders. Given the frequency of these conditions in children and the potential for pediatric use of nizatidine, an oral liquid dosage formulation would provide an alternative treatment option for patients unable to swallow solid oral dosage forms. This study was designed as an open-label, single-dose, four-way crossover trial to investigate the bioequivalence of 150 mg nizatidine administered in three oral liquid formulations (a commercially prepared oral syrup, an extemporaneous solution in apple juice, and an extemporaneous suspension in infant formula) relative to the marketed capsule formulation. Twenty-four adult subjects (ages 31.2 +/- 7.5 years; weight 71.1 +/- 11.8 kg) were enrolled, and blood samples for determination of plasma nizatidine concentrations were collected prior to drug administration and at 19 discrete intervals over a 24-hour postdose interval. Nizatidine was quantitated from plasma using a validated HPLC-MS assay, and a noncompartmental approach was used to describe nizatidine biodisposition in all subjects. Significant treatment effects were observed for log-normalized Cmax, AUC0-n, and AUC0-infinity (p < 0.001). Further evaluation revealed that nizatidine prepared in apple juice was markedly less bioavailable than the reference capsule, with 90% confidence intervals (CIs) of 0.518-0.626, 0.682-0.751, and 0.696-0.763 for Cmax, AUC0-n, and AUC0-infinity, respectively. The remaining two oral formulations demonstrated 90% CI within the guidelines established by the Food and Drug Administration (e.g., 0.80-1.25). Thus, nizatidine in infant formula and the commercially prepared oral syrup can be considered bioequivalent to the reference capsule.
Abdel-Rahman
Susan M
SM
Division of Pediatric Clinical Pharmacology and Medical Toxicology, Children's Mercy Hospital and Clinics, 2401 Gillham Road, Suite 0411, Kansas City, MO 64108, USA.
Johnson
Franklin K
FK
Gauthier-Dubois
Ginette
G
Weston
Irving E
IE
Kearns
Gregory L
GL
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D016567:Nizatidine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D014018:Tissue Distribution
D002214:Capsules; D016567:Nizatidine