An open-label study of the pharmacokinetics and pharmacodynamics of dabigatran etexilate 150mg once daily in Caucasian patients with moderate renal impairment undergoing primary unilateral elective total knee or hip replacement surgery.

BACKGROUND: In adults with moderate renal impairment (creatinine clearance [CrCl] 30-50mL/min) undergoing total hip or knee replacement (THR/TKR), the recommended dose of dabigatran etexilate is 150mg once daily (qd). We investigated the steady state pharmacokinetics, pharmacodynamics and safety in these patients. METHODS: Single-arm, open-label phase 4 study (NCT01184989) in Caucasian patients receiving dabigatran etexilate 75mg 1-4h after surgery and 150mg qd on days 2-10 (TKR) or days 2-35 (THR). Plasma total dabigatran concentrations (day 6±1) were determined by high-performance liquid chromatography tandem mass spectrometry and indirectly using the commercially available diluted thrombin time (dTT) assay (Hemoclot® Thrombin Inhibitors). RESULTS: Of 112 patients (mean CrCl 42.5mL/min, age 79.1years, 69.6% female), 100 completed the study. Geometric mean trough and peak dabigatran concentrations were 47.5ng/mL (10th-90th percentile 19.7-120) and 166ng/mL (49.1-364), respectively. There were four major bleeding events and no venous thromboembolic events. Dabigatran concentrations determined from dTT (and falling within the assay range of 50-500ng/mL) underestimated actual values by 7.6% (90% confidence interval 5.3, 9.9), which is within the acceptance limits of ±15%. CONCLUSIONS: These findings in Caucasians with moderate renal impairment undergoing THR or TKR support the use of the 150mg qd dose of dabigatran etexilate. With adequate set-up, calibration and quality control the dTT assay might be appropriate for situations, such as serious bleeding or a need for urgent surgery, where determination of dabigatran levels would be helpful.

Comparison of phenotypic and genotypic methods for the detection of environmental isolates of Pseudomonas aeruginosa.

During remediation processes, biological monitoring should be generally required. Hydrocarbon contaminated soils may provide favorable conditions for several opportunistic pathogenic microorganisms, thereby increasing their populations over risky levels. Therefore, during remediation processes of the subsurface medium biological monitoring is of prime importance. The accuracy, time and cost efficiency of the relevant identification method are major factors while monitoring these microbes. During previous years (2002-05), we collected 68 soil samples from 17 different oil contaminated sites, such as petrol stations, airfields and pipeline-breaks. We compared frequently applied detection methods of Pseudomonas aeruginosa, both traditional microbiological and molecular biological techniques, on 43 environmental isolates originating from these sites. The following methods were subjected to comparative analysis: (i) the Hungarian Standard method; (ii) the method described in "The Prokaryotes" handbook; (iii) the API 20NE biochemical fingerprinting, as well as PCR protocols aimed to amplify; (iv) the exotoxin-A gene; and (v) the 16S rDNA variable regions V2 and V8. In five cases, phenotypic methods gave false-negative results. 16S rDNA sequence analysis was done to confirm the identity of these five strains, which verified the results of molecular methods. In addition, faults were found in the evaluation of the originally described ETA PCR protocol, which was corrected by us.