Clinical trial: endoscopic evaluation of naproxen etemesil, a naproxen prodrug, vs. naproxen - a proof-of-concept, randomized, double-blind, active-comparator study.

BACKGROUND: Nonsteroidal anti-inflammatory drugs are associated with upper gastrointestinal mucosal injury. Naproxen etemesil is a lipophilic, non-acidic, inactive prodrug of naproxen that is hydrolysed to pharmacologically active naproxen once absorbed. We hypothesized that with lesser topical exposure to naproxen from the prodrug, there would be reduced gastroduodenal mucosal injury compared with naproxen. AIM: To compare the degree of endoscopic mucosal damage of naproxen etemesil vs. naproxen. METHODS: This multicentre, randomized, double-blind, double-dummy trial compared oral naproxen etemesil 1200 mg twice daily (n = 61) with naproxen 500 mg twice daily (n = 59) for 7.5 days in 120 healthy subjects (45-70 years; mean 51 years; 58% female) with baseline total modified gastroduodenal Lanza score ≤ 2 (no erosions/ulcers) on endoscopy. The primary endpoint was mean total modified gastroduodenal Lanza score on day 7. A secondary endpoint was incidence of gastric ulcers. RESULTS: The day 7 mean total modified gastroduodenal Lanza score was 2.8 ± 1.7 for naproxen etemesil vs. 3.5 ± 2.0 for naproxen (P = 0.03), and significantly fewer naproxen etemesil-treated subjects (3.3%) developed gastric ulcers compared with naproxen-treated subjects (15.8%) (P = 0.02). CONCLUSION: In this first proof-of-concept study, naproxen etemesil was associated with significantly lower gastroduodenal mucosal injury compared with naproxen after 7 days of exposure ( CLINICAL TRIAL NUMBER: NCT00750243).

Validated HPLC-MS-MS method for simultaneous determination of atorvastatin and 2-hydroxyatorvastatin in human plasma-pharmacokinetic study.

Cholesterol-reducing statin drugs are the most frequently prescribed agents for reducing morbidity and mortality related to coronary heart disease. In this publication a validated, highly sensitive, and selective isocratic HPLC method is reported for quantitative determination of the major statin drug atorvastatin (ATV) and its metabolite 2-hydroxyatorvastatin (HATV). Detection was performed with an electrospray ionization triple-quadrupole mass spectrometer equipped with an ESI interface operating in positive-ionization mode. Multiple reaction monitoring (MRM) was used for MS-MS detection. The calibration plot was linear in the concentration range 0.10-40.00 ng mL(-1) for both ATV and HATV. Inter-day and intra-day precision and accuracy of the proposed method were characterized by measurement of relative standard deviation (RSD) and percentage deviation, respectively; both were less than 8% for both analytes. The limit of quantitation was 0.02 ng mL(-1) for ATV and 0.07 ng mL(-1) for HATV. The method was used for pharmacokinetic study of ATV and HATV. Pharmacokinetic data for all analytes are also reported.

[Acute anxiety and its therapy]. / Akutní úzkost a její lécba.

Acute anxiety is a quite common event for a general practitioner to solve. Anxiety could be of a various ethiology and the treatment should be based on the ethiology. It is important to differentiate panic attacks from general anxiety so as panic disorder treatment differs specifically. The drug of choice for parenteral application for acute anxiety seems to be diazepam in the Czech republic conditions and the most convenient drug for oral administration is alprazolam.

Pharmacokinetics and metabolism of [3H]-pipethiaden in healthy volunteers.

Six healthy volunteers participated in a single-dose study of pharmacokinetics and metabolism of oral administration of [3H]-pipethiaden (1 mg). Plasma levels of total radioactivity, urinary excretion and metabolism were analyzed by liquid scintillation counting and radio-TLC. The mean peak plasma concentration of radioactive metabolites was 4.9 ng eq/ml, and the mean elimination half life was 11.5 h. 34% of radioactivity was recovered in 4 days in urine, with only 0.4% present as unchanged drug. Pipethiaden was extensively metabolized by S-oxidation, N-demethylation, and N-oxidation.

[Determination of the oxidation phenotype in the Czechoslovak population using metoprolol]. / Stanovení oxidacního fenotypu metoprolem v nasí populaci.

The authors assessed the oxidative phenotype type debrisochin/spartein in 97 healthy volunteers aged 23 to 56 years (45 men and 52 women). After metoprolol administration which served as a model substance, in doses of 100 mg p. o. at night, the authors collected urine during 8 hours. In the urine specimens they assessed by gas chromatography with detection of the electron capture (fig. 1) the metabolic ratio of metoprolol/alpha-hydroxymetoprolol (M/HM). The distribution of logM/HM on the frequency histogram was bimodal and made it possible to divide the group into extensive and poor metabolizers (fig. 2). The authors detected 6 poor metabolizers which corresponds to the results in the white population. The authors discuss the clinical impact of oxidative polymorphism in the treatment with metoprolol, diltiazem, quinidine and other drugs.

Three years experience with local hydrocortisone treatment in women with immunological cause of infertility.

Two high selected groups of infertile women with proved cervical spermagglutinating antibodies by ficin, sucrose gradient ultracentrifugation, ELISA and microagglutinating test, by indirect MAR-test had been chosen for local hydrocortisone treatment. In the first group being composed of 20 infertile women we registered 16 decreasing or total disappearance of antisperm activity in cervical ovulatory mucus. Ten of them delivered healthy child. New 27 selected patients have treated in their immunological failure of reproduction by local hydrocortisone application, too, two of them are pregnant now. During the local hydrocortisone immunosuppression no side effects were registered. Hydrocortisone treatment seems to be a very perspective method in regulation of cervical immunological cause of infertility.

Local hydrocortisone treatment of sperm-agglutinating antibodies in infertile women.

Local sperm-agglutinating antibodies (LSAA) in the cervical ovulatory mucus may be a cause of primary infertility. A group of 17 infertile women with LSAA treated without effect with artificial insemination and then condom therapy were studied. After hydrocortisone application to the ectocervix for up to four cycles, LSAA disappeared totally in 13 patients; six of them have given birth to babies. No side effects of treatment were observed. Hydrocortisone for local immunosuppression may become a new method of therapy in cervical immunological infertility.