Influence of tobacco smoke on the pharmacokinetics of citalopram and its enantiomers

The purpose of this study was to evaluate the influence of tobacco smoke on the pharmacokinetics of citalopram (CIT) and desmethylcitalopram (DCIT) and its enantiomers on an animal model. High performance liquid chromatography (HPLC) with a diode array detector (DAD) was used for the identification and quantification of the studied compounds. The HPLC quantification of racemic mixtures of CIT was performed on a C18 column. The limits of detection (LOD) and quantification (LOQ) were: 7 and 10 ng/ml respectively. HPLC separation of citalopram enantiomers (S- and R-CIT) was performed on a Chirobiotic V column. The limits of detection (LOD) and quantification (LOQ) were: 6 and 15 ng/ml for R- and S-CIT respectively. The experiment was carried out on male Wistar rats. The rats were exposed to tobacco smoke for five days (6 hours per day). After the exposure, citalopram was administered in a dose of 10 mg/kg intragastrically. In the control group (non-exposed animals), citalopram was administered in the same way and at an equal dose. The blood of the animals was collected at nine time points. It was found that tobacco smoke exposure inhibits the biotransformation of citalopram. The half-life of the racemic mixture of citalopram after intragastric administration was increased by about 287%. Changes in the pharmacokinetic parameters of S-citalopram (active isomer) show a similar tendency to those of the racemic mixture. The pharmacokinetics of R-citalopram showed no statistically important differences after tobacco smoke exposure. Alterations in the pharmacological parameters of desmethylcitalopram presented an opposite trend to the parent drug. After exposure to tobacco smoke, the induction of metabolism of this compound was observed

Diazepam and its metabolites in the mothers' and newborns' hair as a biomarker of prenatal exposure

Pregnant women are exposed to benzodiazepines for therapeutic purposes during gestation. The goal of this study was to evaluate prenatal exposure to benzodiazepines. Time of exposure during course of pregnancy is a significant aspect of fetal exposure to drugs. Benzodiazepine concentration assay in hair of mothers and newborns exposed prenatally to these drugs was performed in the studies. Development, validation and evaluation of benzodiazepine determination method in mothers and their newborns enables assessment of health risks for the child and implementation of adequate therapeutic procedures. We used A LC-ESI-MS/MS method that allowed determination of diazepam (the main benzodiazepine used by pregnant women was diazepam) and its metabolites (nordazepam, oxazepam) in hair of mothers and newborns. LOQ 10 pg/mg of hair was used in the study. Results: concentration of nordazepam was higher than parent drug (diazepam) and higher in newborns’ hair when compared to mothers’. The mean concentrations of diazepam in mothers’ hair were 31.6±36.0 and 34.1±42.4 pg/mg in the second and third trimester of pregnancy respectively. The mean concentration of diazepam in newborns’ hair was higher and reached levels of 53.3±36.5 pg/mg. The mean concentration of nordazepam in the mothers’ hair corresponding to the second and third trimester was 52.9±48.1 and 89.9±122.8 pg/mg, respectively. Nordazepam in the newborns’ hair was detected at the mean level of 108.1±144.2 pg/mg. It was concluded that diazepam and nordazepam are permanently incorporated into the hair structure. Presence of diazepam and its metabolites in newborn’s hair confirms that these benzodiazepines permeate placental barrier. Segmental analysis of mothers’ hair enabled the assessment of drug administration time. Diazepam and its metabolites determined in hair of newborns may serve as biomarkers of prenatal exposure to these drugs. The performed LC-MS/MS analysis was accurate enough to determine even low concentrations of benzodiazepines, at the level of few pg/mg of hair. Levels of diazepam detected in hair of newborns were higher than levels determined in mothers. This may confirm the fact, that fetus’s ability to metabolize diazepam is scarce. Nordazepam was found in higher concentrations in hair of newborns than in hair of mothers, which may suggest that it is cumulated in child’s organism. Other metabolites of diazepam - oxazepam and temazepam - were detected in very few cases, in low concentrations

Utilization of Basalt Dust as Waste Material in Cement Grouts for Geothermal Application

Research on the utilization of the Earth’s heat focuses mainly on effective sourcing of energy accumulated in rock mass. One of the most important parameters is thermal conductivity, which can be modified using various compositions of cement grouts. Hardened cement slurry is intended to improve thermal conductivity. It should function as a sort of extension of the rock mass to the outer diameter of heat exchanger tubes. Regardless of the thermal conductivity of the rock, high conductivity of the grout increases the energy efficiency of the BHE. Heat accumulated in the rock mass can be extracted using borehole heat exchangers (BHE), in which high thermal conductivity of cement slurry is wanted over the entire length of the exchanger. Generally, in case of deep borehole heat exchangers (DBHE), it is recommended to use two types of cement slurry, one with reduced thermal conductivity in the upper part of the exchanger and grout with increased thermal conductivity in its lower part. When cementing geothermal wells, cement grout with decreased thermal conductivity along the entire length of the borehole is most commonly used. Geothermal boreholes extract geothermal water which, at the surface, is used for heating, for example. Then, after use, the cooled water is injected through injection holes. In this article, two different basalt dusts are examined. These dusts were obtained by crushing basalt boulders in open-pit mines. They were examined for their effect on thermal conductivity when added to grout. According to the Polish Ordinance of the Minister of Environment dated 9 December 2014 regarding the waste catalogue, they were classified as waste. The materials, named basalt dust A and basalt dust B, were used to create cement slurries with a water–cement ratio of 0.5–0.7 with a wide range of percentage concentration of basalt dust. The test results show that as concentrations in the slurry increase, the values of thermal conductivity and strength decrease. This correlation occurred for both tested additives

Utilization of Basalt Dust as Waste Material in Cement Grouts for Geothermal Application

Research on the utilization of the Earth’s heat focuses mainly on effective sourcing of energy accumulated in rock mass. One of the most important parameters is thermal conductivity, which can be modified using various compositions of cement grouts. Hardened cement slurry is intended to improve thermal conductivity. It should function as a sort of extension of the rock mass to the outer diameter of heat exchanger tubes. Regardless of the thermal conductivity of the rock, high conductivity of the grout increases the energy efficiency of the BHE. Heat accumulated in the rock mass can be extracted using borehole heat exchangers (BHE), in which high thermal conductivity of cement slurry is wanted over the entire length of the exchanger. Generally, in case of deep borehole heat exchangers (DBHE), it is recommended to use two types of cement slurry, one with reduced thermal conductivity in the upper part of the exchanger and grout with increased thermal conductivity in its lower part. When cementing geothermal wells, cement grout with decreased thermal conductivity along the entire length of the borehole is most commonly used. Geothermal boreholes extract geothermal water which, at the surface, is used for heating, for example. Then, after use, the cooled water is injected through injection holes. In this article, two different basalt dusts are examined. These dusts were obtained by crushing basalt boulders in open-pit mines. They were examined for their effect on thermal conductivity when added to grout. According to the Polish Ordinance of the Minister of Environment dated 9 December 2014 regarding the waste catalogue, they were classified as waste. The materials, named basalt dust A and basalt dust B, were used to create cement slurries with a water–cement ratio of 0.5–0.7 with a wide range of percentage concentration of basalt dust. The test results show that as concentrations in the slurry increase, the values of thermal conductivity and strength decrease. This correlation occurred for both tested additives

The effects of tobacco smoke exposure on caffeine metabolism

Caffeine and nicotine are some of the most often self-administered substances worldwide. Very often they are taken simultaneously and it seems that this fact is correlated with the amount of caffeine and nicotine administered. The aim of this study is to determine, whether tobacco smoke influences the metabolism of caffeine. The secondary task is to establish whether caffeine has an effect on elimination of cotinine, nicotine’s main metabolite. The results showed that tobacco smoke influences the metabolism of caffeine by accelerating its elimination, by the means of induced CYP1A2 activity. As far as cotinine is concerned, no influence of caffeine on its elimination was observed