Effects of excessive alcohol drinking on nicotine biotransformation in rats

Alcohol and nicotine (tobacco smoke) are often used together, and taking both addictive substances is associated with an increased risk of certain diseases. It is extremely important to understand the pharmacodynamic and pharmacokinetic mechanisms of the interaction between nicotine and ethanol, which are still not fully understood. The study aimed to evaluate the influence of chronic alcohol consumption on nicotine biotransformation in ethanol-preferring and non-preferring male and female rats. Rats were divided into four groups depending on their alcohol preferences and gender. Nicotine, nornicotine, nicotine N-oxide, cotinine, trans-3'-hydroxycotinine, and cotinine N-oxide in rats plasma were determined by LC–MS/MS after five days of exposure to tobacco smoke. A non-compartmental analysis of nicotine and its metabolites was used for pharmacokinetic parameters calculation. Our experimental results showed that the rate of nicotine elimination depends on gender, regardless of alcohol preferences (significantly slower in females than in males). Mean residence timeof nornicotine, cotinine, and trans-3'-hydroxycotinine were significantly higher in alcohol-preferring male rats than in alcohol preferring female rats. In non-alcohol preferring female rats compared to ethanol-preferring female rats, significantly more nicotine N-oxide (fivefold) and trans-3'-hydroxycotinine (twofold) reached the general circulation unchanged. Drinking ethanol influenced the elimination of nornicotine and cotinine in male rats. Ethanol consumption was identified as a modifier of nicotine pharmacokinetics and this was gender-dependent

Radiation sterilization of ephedrine in the solid state

The effects of the e-beam ionising radiation of energy 9.96 MeV in doses 25 800 kGy on the stability of solid ephedrine hydrochloride (1R,2S)-(-)-2-methylamino-1-phenyl-1-propanol hydrochloride) have been studied. These effects have been observed using the following analytical methods: organoleptic (form, colour, smell, clarity of solution), scanning electron microscope SEM, pH measurement, chirality and water content measurement (Karl Fischer method), spectrometric methods (UV, FT IR, EPR), chromatography (TLC), and combined chromatography (TLC UV, GC MS). Even the standard sterilisation dose of 25 kGy has been found to cause a change in colour from white to pale yellow, the appearance of free radicals in the concentration of 3.05×10^15 spin/g, and about 1% loss of the content. The effects of higher doses 50 800 kGy have shown that radiodegradation degree of the compound is proportional to the dose applied. The main product of radiodegradation, formed at a yield of G = 17.17×10^7 mol/J, has been identified as 2-methylamino-1 phenyl-1-propanone (methcathinone, ephedrone), a psychoactive compound of the activity similar to that of amphetamine. For the above reasons ephedrine hydrochloride can not be subjected to radiative sterilisation with a dose of 25 kGy, however, assuming sufficiently low microbiological contamination of the initial substance, lower doses could be probably used for sterilisation purposes. Our results have not confirmed the earlier reports from 1970s on the resistance of ephedrine to ionising radiation in doses up to 60 kGy

Midazolam and hydroxymidazolam plasma concentrations can be monitored with selected biochemical and physiological parameters of palliative care patients

Rationale &amp; objective: Midazolam is one of top three drugs used in palliative care. Its use increases in the last days of hospice patients’ lives while safe dosage can be challenging. Equations currently used to estimate glomerular filtration rate, e.g: the Cockroft-Gault (eGFRCR) and the Modification of Diet in Renal Disease (eGFRMDRD) ones, do not generate precise calculations, especially in palliative patients exhibiting variations in body parameters. Our aim was to seek new relationships between mean midazolam (Mavg) and alfahydroxymidazolam (OH-Mavg) concentrations in plasma, and selected biochemical and physiological parameters of palliative patients, to enable optimal midazolam pharmacotherapy. Study design, participants and interventions: The pilot study included 11 Caucasians, aged 42–95, with advanced cancer disease, receiving midazolam in a hospice in-patient unit. We tested correlations among Mavg, BMI, eGFRMDRD, midazolam clearance (CL), OH-Mavg, bilirubin (Bil) and blood creatinine concentration (Cr). F test and leave-one out (LOO) validation was applied to verify the correlations’ significance and predictive ability. Results: We found ten statistically significant (p < 0.05) correlations related to midazolam pharmacokinetics and physiological factors. We formulated two equations with high degree of predictive ability, based on the eGFRMDRD→CL and the (Bil + BMI × Ln(Cr))→Mavg-(OH-Mavg) correlations.The limitations of the study mainly revolve around its pilot nature and the need to continue testing the results on a bigger population.No funding to disclose. Conclusions: The significance of correlations corresponding to the arithmetic expressions confirms that Bil, BMI, Ln(Cr) analyzed simultaneously report a series of processes on which midazolam metabolism depends. Two of ten correlations proposed came close to meet all LOO validation criteria. Current findings can help optimize midazolam treatment in palliative therapy

Influence of extracts from Rhodiola rosea and Rhodiola kirilowii on the development of alcohol tolerance in rats

Introduction:Rhodiola rosea (RR) and Rhodiola kirilowii (RK) are well known for their influence on central nervous system, however their impact on the development of alcohol tolerance has not yet been proven