• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.113-121
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• 1998

To clarify whether nizatidine, a $H_2$ receptor antagonist, has the cholinergic activity, the effects of nizatidine on the guinea pig ileum and on the acetylcholinesterase in human serum were studied. And, the mechanism of excitatory effect of nizatidine on the cholinergic system in ileum was also studied. Nizatidine caused a concentration-dependent contractile response by the guinea pig ileum. The $EC_{50}\;was\;53\;{\mu}M$ and the maximum response was at $300\;{\mu}M$. Ranitidine also caused a contractile response by the guinea pig ileum, but cimetidine and famotidine did not. The pretreatment with $H_1$ receptor antagonist did not affect the actions of nizatidine on the guinea pig ileum, but the pretreatment with atropine completely blocked them. Nizatidine significantly enhanced the acetylcholine-induced response of the guinea pig ileum, but not the pilocarpine-induced response. Nizatidine did not affect the histamine-induced response of the guinea pig ileum. Nizatidine still exerted the small excitatory effect on the guinea pig ileum pretreated with the high concentration of physostigmine. Nizatidine significantly inhibited the acetylcholinesterase in human serum. These results suggest that nizatidine exerts an excitatory effect on guinea pig ileum which seems to be associated with the cholinergic system, probably through an indirect mechanism, inhibition of acetylcholinesterase and/or increased release of acetylcholine.

• Journal of Pharmaceutical Investigation
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• v.34 no.1
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• pp.43-48
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• 2004

The purpose of the present study was to evaluate the bioequivalence of two nizatidine capsules, Axid (Lilly Korea Pharm. Co., Ltd.) and Nex (Bi-nex Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The nizatidine release from the two nizatidine capsules in vitro was tested using KP Apparatus method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solutions and water). The dissolution prefers of two nizatidine capsules were very similar at all dissolution media. Twenty four normal male volunteers were divided into two groups with a randomized 22 crossover study. After two capsules (300 mg nizatidine) were orally administrated, blood was taken and the concentrations of nizatidine in serum were determined using HPLC with UV detector. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were determined. The result showed that the differences in $AUC_t$, $C_{max}$ and $T_{max}$ between two nizatidine capsules based on the Axid were -6.16%, -8.26% and -1.82%, respectively. There were no sequence effects between two capsules in these parameter. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(125)(e.g., $log(0.91){\sim}log(0.97)$ and $log(0.85) {\sim}log(0.99)$ for $AUC_t$ and $C_{max}$ respectively), indicting that Nex capsule is bioequivalent to Axid capsule.

• Korean Journal of Bronchoesophagology
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• v.9 no.1
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• pp.67-74
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• 2003

Larygopharyngeal reflux(LPR) is one form of the Gastroesophageal Reflux Diseases(GERD). It is known to cause various kinds of otolaryngologic symptoms such as hoarseness, globus sensation in throat, chronic throat clearing, and chronic cough, Disease entities diagnosed by otolaryngologists as posterior laryngitis, globus pharyngeus and reflux laryngitis should be suspected as LPR-related diseases. The nizatidine(AXID), as a Histamine H2-receptor antagonist, reduces gastric acid secretion and improves gastric motility function. Objectives : The effect of nizatidine using 150mg b.i.d was evaluated for symptom relief and improvement of laryngoscopic findings in patients with LPR. Materials and Methods : In 30 multicenter, observational trial performed nationalwidely in Korea. 308 patients with LPR symptom were observed to evaluate their symptoms and larygnoscopic findings after 4weeks, 8weeks, 12weeks of treatment with nizatidine. Results : The symptoms of LPR including globus sensation, chronic throat clearing and hoarseness, are reduced significantly after 4 weeks, 8weeks, and 12weeks of treatment(p<0.05). The laryngoscopic findings including diffuse erythema, edema and granulation are improved after nizatidine treatment(p<0.05). and the efficacy of nizatidine on LPR-related sympoms after 4 weeks is 88.6%, and those of after 8 weeks and 12weeks were 92.6%, and 99.1% in ITT(Intent To Treatment) group(p<0.05). And PPA(Per Protocol Analysis)group showed 93.7%, 97.3%, and 99.1% of efficacy after 4, 8, and 12 weeks of nizatidine treatment(p<0.05). Conclusion : These results indicate that in patient with LPR, nizatidine 150mg b.i.d treatment very effectively reduces LPR symptoms and improves laryngoscopic findings as well as reduces gastric acid secretion and improves gastric motility function.

• Archives of Pharmacal Research
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• v.27 no.7
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• pp.720-726
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• 2004

Two Spectrophotometric procedures are presented for the determination of two commonly used H2-receptor antagonists, nizatidine (I) and ranitidine hydrochloride (II). The methods are based mainly on charge transfer complexation reaction of these drugs with either ${\rho}-chloranilic$ acid (${\rho}-CA$) or 2, 3 dichloro-5, 6-dicyanoquinone (DDQ). The produced colored products are quantified spectrophotometrically at 515 and 467 nm in chloranilic acid and 000 methods, respectively. The molar ratios for the reaction products and the optimum assay conditions were studied. The methods determine the cited drugs in concentration ranges of 20-200 and $20-160\;\mu\textrm{g}/mL$ for nizatidine and ranges of 20-240 and $20-140\;\mu\textrm{g}/mL$ for ranitidine with chloranilic acid and DDQ methods, respectively. A more detailed investigation of the complexes formed was made with respect to their composition, association constant, molar absorptivity and free energy change. The proposed procedures were successfully utilized in the determination of the drugs in pharmaceutical preparations. The standard addition method was applied by adding nizatidine and ranitidine to the previously analyzed tablets or capsules. The recovery of each drug was calculated by comparing the concentration obtained from the spiked mixtures with those of the pure drug. The results of analysis of commercial tablets and the recovery study (standard addition method) of the cited drugs suggested that there is no interference from any excipients, which are present in tablets or capsules. Statistical comparison of the results was performed with regard to accuracy and precision using student's t-test and F-ratio at 95％ confidence level. There is no significant difference between the reported and proposed methods with regard to accuracy and precision.

• Proceedings of the Korean Society of Life Science Conference
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• 2003.10a
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• pp.60-61
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• 2003