Potential factors of Helicobacter pylori resistance to clarithromycin.

OBJECTIVES: A comparative dissolution kinetics test (CDKT) and bioequivalence studies of generic proton pump inhibitors (PPIs) do not model pharmacological acid suppression (PAS) and pathological duodenogastric reflux (PDGR). This study aimed to model them in CDKT to assess drugs stability and potential pantoprazole-clarithromycin interactions. METHODS: In CDKT, PDGR (dissolution medium pH 7.00 ± 0.05, preexposure at pH 1.20 ± 0.05) and PAS (pH 4.00 ± 0.05) were modelled for original pantoprazole (OP) and its generics (GP1-4). In CDKT with high-performance liquid chromatography, dissolution gastric medium in adequate (pH 4.00 ± 0.05) and inadequate (pH 1.20 ± 0.05) PAS were modelled for original clarithromycin (OC) and its generics (GC1-4). RESULTS: After exposure in pH 7.00 ± 0.05, pantoprazole was released from GP1 within 10 min in the amount of 68.8%. In рН 4.00 ± 0.05, 83.0% and 81.5% of pantoprazole were released from GP1 and GP4. When OP, GP2 and GP3 were placed in pH 7.00 ± 0.05, pantoprazole was released in amount: 99.4%, 88.0% and 98.2%. Clarithromycin releasing from OC, GC1, GC2, GC3, GC4 in pH 4.00 ± 0.05 was 93.5%, 91.6%, 92.9%, 79.4% and 83.0%. In pH 1.20 ± 0.05: 9.7%, 6.7%, 8.5%, 33.3%, 28.8%. CONCLUSIONS: Destruction of enteric coats of some local pantoprazole generics in CDKT-models might be a potential factor for inadequate therapy.

A study of the pharmacokinetics of moxifloxacin by the dynamics of its distribution in the blood plasma and saliva of healthy volunteers: a comparative analysis and possible extrapolation methods.

Objectives The pharmacokinetics of moxifloxacin in plasma and saliva was investigated in this study. Methods The pharmacokinetics of two specialty drugs of moxifloxacin - reference (Ref) and test (Test) preparation - was studied in 18 healthy volunteers after a single oral dose of 400 mg. Results It was found that the concentration of moxifloxacin in saliva 3-24 h after taking the drugs was statistically significantly higher than that in plasma. A high correlation was observed between the concentration of moxifloxacin in plasma and saliva of volunteers after taking of Ref and Test. Some pharmacokinetic parameters, calculated by the concentration of moxifloxacin in saliva and plasma, are statistically different. A technique is proposed for extrapolating the concentration of moxifloxacin in plasma according to its concentration in saliva using the established linear relationship between the moxifloxacin in plasma and saliva of volunteers in time interval of 3-24 h after taking Ref. Based on the obtained extrapolated concentration of moxifloxacin, the pharmacokinetic parameters were calculated for two studied drugs and did not statistically differ from the parameters calculated according to the data in plasma. Conclusions The developed method of concentration extrapolation allows the use of saliva for pharmacokinetic studies of the tablet preparations of moxifloxacin.

A study of the pharmacokinetics of moxifloxacin by the dynamics of its distribution in the blood plasma and saliva of healthy volunteers: a comparative analysis and possible extrapolation methods.

OBJECTIVES: The pharmacokinetics of moxifloxacin in plasma and saliva was investigated in this study. METHODS: The pharmacokinetics of two specialty drugs of moxifloxacin - reference (Ref) and test (Test) preparation - was studied in 18 healthy volunteers after a single oral dose of 400 mg. RESULTS: It was found that the concentration of moxifloxacin in saliva 3-24 h after taking the drugs was statistically significantly higher than that in plasma. A high correlation was observed between the concentration of moxifloxacin in plasma and saliva of volunteers after taking of Ref and Test. Some pharmacokinetic parameters, calculated by the concentration of moxifloxacin in saliva and plasma, are statistically different. A technique is proposed for extrapolating the concentration of moxifloxacin in plasma according to its concentration in saliva using the established linear relationship between the moxifloxacin in plasma and saliva of volunteers in time interval of 3-24 h after taking Ref. Based on the obtained extrapolated concentration of moxifloxacin, the pharmacokinetic parameters were calculated for two studied drugs and did not statistically differ from the parameters calculated according to the data in plasma. CONCLUSIONS: The developed method of concentration extrapolation allows the use of saliva for pharmacokinetic studies of the tablet preparations of moxifloxacin.

Comparative study of the bioavailability of magnesium salts.

Background High values of endogenous levels of magnesium (Mg) in the body and mechanisms of homeostasis regulation make it difficult to assess the bioavailability of these drugs. The aim of this study was to assess the Mg concentration in blood in volunteers and in erythrocytes in patients with hypomagnesemia. Methods The study included 20 healthy volunteers and 62 patients with chronic heart failure (CHF) I-III functional class (FC) NYHA classification. We studied the composition of Mgorotate and Mgorotate plus potassium (К)orotate. Blood sampling was carried out at 8 a.m. and within 10 h after administering the drugs. Measurement of Mg pharmacokinetic parameters: AUC (concentration of the active substance-time), and Cmax (maximum concentration) in volunteers and measurement of the concentration of Mg in erythrocytes of patients. Results The results indicated that both the AUC in volunteers and concentration of Mg in erythrocytes of patients are comparable, and the differences are not statistically significant. Conclusions The study showed that the standard method of calculating the AUC (total serum Mg) is insufficient for comparative evaluation of Mg absorption due to the high levels of its endogenous content and a small increase in concentration after taking the drugs. It is advisable to assess the concentration of Mg in the red blood cells of patients.

The influence of taurine and L-carnitine on 6 ß-hydroxycortisol/cortisol ratio in human urine of healthy volunteers.

Background Cytochrome P450s (CYPs, EC 1.14.14.1) are the main enzymes of drug metabolism. The functional significance of CYPs also includes the metabolism of foreign chemicals and endogenic biologically active compounds. The CYP3A4 isoform contributes to the metabolism of about half of all marketed medicinal preparations. The aim of this study was to investigate the effects of two biologically active compounds: 2-aminoethane-sulfonic acid (taurine) and 3-hydroxy-4-trimethylaminobutyrate (L-carnitine) on urinary 6ß-hydroxycortisol/cortisol (6ß-OHC/cortisol) metabolic ratio as a biomarker of the CYP3A4 activity of healthy volunteers. Taurine is used for the treatment of chronic heart failure and liver disease. Cardiologists, nephrologists, neurologists, gerontologists in addition to the main etiopathogenetic therapies, use L-carnitine. The quantification of the 6ß-OHC/cortisol metabolic ratio as a biomarker of CYP3A4 activity in human urine was used for the assessment of CYP3A4 catalytic activity as a non-invasive test. Methods The study included 18 healthy male volunteers (aged from 18 to 35 years old). The volunteers took taurine in a dose of 500 mg twice a day or L-carnitine in a dose of 2.5 mL 3 times a day for 14 consecutive days. The test drug was given 20 min before meals. The collection of urine samples was performed before and after 3, 7, 10, and 14 days after taurine intake. The metabolic ratio of 6ß-OHC/cortisol in morning spot urine samples was studied by the liquid chromatography/mass spectroscopy (LC/MS) method. Results The ratio of 6-6ß-OHC/cortisol was used as a biomarker to study the taurine and L-carnitine influence on CYP3A4 metabolism of cortisol. The ratio of urinary 6ß-OCH/cortisol in the morning urine samples of volunteers before the beginning of taurine therapy (baseline ratio) was 2.71 ± 0.2. Seven days after the administration of taurine in a dose of 500 mg twice a day, the 6ß-OCH/cortisol ratio was 3.3 ± 0.2, which indicated the increased catalytic activity of CYP3A4 towards cortisol. As for the L-carnitine supplementation, analysis of the 6ß-OCH/cortisol ratio in the urine for 14 days did not show any significant changes in this baseline ratio, indicating the lack of L-carnitine influence on the catalytic activity of CYP3A4 to cortisol. Conclusions The results obtained demonstrated the influence of taurine on 6ß-OCH/cortisol metabolic ratio as a biomarker of CYP3A4 catalytic activity to cortisol. L-carnitine did not affect the activity of CYP3A4. The lack of a clinically meaningful effect of L-carnitine was established.