In the 1980-90s numerous studies were performed on H2-receptor antagonist inhibition of ethanol first pass metabolism. Blood alcohol concentrations warranting possible driving under the influence citations in the United States have subsequently dropped from ≥ 100 mg/dL to 50 mg/dL (Utah in 2019) (30 mg/dL or zero tolerance in some parts of the world). A reexamination of these studies seemed important. Areas covered: Papers were compiled that addressed the effect of cimetidine, ranitidine, famotidine, and nizatidine on ethanol metabolism first from a PubMed search and then from citations within these papers. Studies were tabulated for fasting versus fed, ethanol and H2-receptor antagonist dose and a summary of pharmacokinetic changes. Expert opinion: At doses of 0.15-0.30 mg/kg in the postprandial state (primarily after breakfast), the H2-receptor antagonists: cimetidine, ranitidine, famotidine, and nizatidine have all been found to increase the first pass metabolism of ethanol. With cimetidine there were sufficient studies to suggest it might be inhibitory outside these restricted states. While the role of inhibition of alcohol dehydrogenase has not been clearly defined there is circumstantial evidence to support this mechanism. Further studies are required to elucidate the ability of H2-receptor antagonists to inhibit first pass metabolism of ethanol.

Because of the low levels of nizatidine in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. No special precautions are required. Histamine H2-antagonists with more extensive use might be preferred in newborns.

Nizatidine has been labeled using [125 I] with chloramine-T as oxidizing agent. Factors such as the amount of oxidizing agent, amount of substrate, pH, reaction temperature, and reaction time have been systematically studied to optimize the iodination. Biodistribution studies indicate the suitability of radioiodinated nizatidine as a novel tracer to image stomach ulcer. Radioiodinated nizatidine may be considered a highly selective radiotracer for peptic ulcer imaging.

A comparative force degradation high performance thin layer chromatography (HPTLC) method was developed and validated for some H2-receptor antagonists. The studied H2-receptor antagonists were ranitidine (RAN), nizatidine (NIZ) and famotidine (FAM). The degradation behaviors of the studied H2-receptor antagonists were studied under different stress conditions (hydrolytic, thermal and oxidative) conditions as well as storage conditions according to International Conference on Harmonization (ICH) recommendations. A stability-indicating HPTLC method was optimized in order to separate the analyte from the degradation products formed under various stress conditions. Full separation of the drugs from their degradation products was successfully achieved on an HPTLC precoated silica gel plates. Densitometric measurements were carried out using a Camag TLC Scanner III in the absorbance mode at 320 nm for RAN and NIZ, and 280 nm for FAM. The limits of detection and limits of quantitation range were 5.47-9.37 and 16.30-31.26 ng/band, respectively, for all investigated drugs. The validation studies were performed according to ICH requirements. The developed method was simple, rapid and reliable hence it could be applied for routine quality control analysis of the investigated H2-receptor antagonists in dosage forms. The kinetic behavior, degradation rate constants and half-lives of the degradation of the investigated drugs were studied and compared at different stress conditions. The present study provides, for the first time, a new vision to compare the degradation kinetics of H2-receptor antagonists at the same degradation procedures.

This study investigated the degradation kinetics and halonitromethanes formation potential (HNMsFP) of two nitro-based pharmaceuticals (i.e., ranitidine (RNTD) and nizatidine (NZTD)) during ultraviolet (UV) photolysis. It was found that the degradation kinetics of RNTD and NZTD exhibited pH-dependent trends, in accordance with their deprotonation equilibria. The neutral species of RNTD and NZTD were more photo-reactive than their corresponding deprotonated species, with their specific fluence-based first-order rate constants varying in the range of 5.64-31.90 m(2) E(-1). Both the RNTD and NZTD were prone precursors of HNMs (with molar yields of 5.6± 0.3% and 4.7± 0.4%, respectively at pH 7.0). Acidic and neutral circumstances facilitated the HNMs formation. The UV photolysis of RNTD and NZTD could reduce their HNMsFP simultaneously. Positive linear relationships between residual RNTD or NZTD concentration and HNMsFP were observed and the denitration during the UV photolysis accounted for the HNMsFP reduction. With the mandatory UV disinfection fluences in China (i.e. 20-80 mJ cm(-2)), the effective abatement of RNTD and NZTD and their HNMsFP could not be fully achieved, highlighting the necessity of increasing UV fluence or developing UV-based advanced oxidation process in future.

The dielectric properties of two pharmaceuticals nizatidine and perphenazine were investigated in the supercooled liquid and glassy states by broadband dielectric spectroscopy. Two relaxation processes were observed in both the pharmaceuticals. The relaxation process observed above the glass transition temperature is the structural alpha relaxation and below the glass transition temperature is the gamma relaxation of intramolecular origin. The Johari-Goldstein beta relaxation coming from the motion of the entire molecule is found to be hidden under the structural relaxation peak in both the pharmaceuticals.

The slow molecular mobility in the amorphous solid state of 3 active pharmaceutical drugs (cimetidine, nizatidine, and famotidine) has been studied using differential scanning calorimetry and the 2 dielectric-related techniques of dielectric relaxation spectroscopy and thermally stimulated depolarization currents. The glass-forming ability, the glass stability, and the tendency for crystallization from the equilibrium melt were investigated by differential scanning calorimetry, which also provided the characterization of the main relaxation of the 3 glass formers. The chemical instability of famotidine at the melting temperature and above it prevented the preparation of the amorphous for dielectric studies. In contrast, for cimetidine and nizatidine, the dielectric study yielded the main kinetic features of the α relaxation and of the secondary relaxations. According to the obtained results, nizatidine displays the higher fragility index of the 3 studied glass-forming drugs. The thermally stimulated depolarization current technique has proved useful to identify the Johari-Goldstein relaxation and to measure τβJGin the amorphous solid state, that is, in a frequency range which is not easily accessible by dielectric relaxation spectroscopy.

The histamine H₂-receptor antagonists cimetidine, famotidine and nizatidine are individually encapsulated by macrocyclic cucurbit[7]uril (CB[7]), with binding affinities of 6.57 (±0.19) × 10³ M(-1), 1.30 (±0.27) × 10⁴ M(-1) and 1.05 (±0.33) × 10⁵ M(-1), respectively. These 1:1 host-guest inclusion complexes have been experimentally examined by ¹H-NMR, UV-visible spectroscopic titrations (including Job plots), electrospray ionization mass spectrometry (ESI-MS), and isothermal titration calorimetry (ITC), as well as theoretically by molecular dynamics (MD) computation. This study may provide important insights on the supramolecular formulation of H₂-receptor antagonist drugs for potentially enhanced stability and controlled release based on different binding strengths of these host-guest complexes.