In clinical trials adverse events improve after dose reduction suggesting a dose-dependent toxicity. Given dose has a direct impact on the drug serum concentration, but the latter also can be influenced by multiple factors including interaction and metabolization. To enable the investigation of concentration related effects, an easy and sensitive assay for sorafenib drug monitoring is essential.
Methods:A high performance liquid chromatography (HPLC) analysis involving an extraction with diethyl ether followed by separation on a Pinnacle™ DB C18 column and quantitation by UV absorbance at 260 nm was established. Sorafenib concentrations in samples of serum and peritoneal fluid have been determined.
Results:The assay was validated for serum samples and is linear over the concentration range of 100 to 5000 ng/mL with a determination coefficient of >0.999. The limit of detection is 0.25 ng/mL. The intra-and inter-day coefficients of variation were below 3.03%. Sorafenib recovery in spiked probes of peritoneal fluid was above 85 %. Sorafenib concentrations in 44 serum samples and 14 probes of peritoneal fluid have been determined with a mean of 3328 and 1380 ng/mL respectively (standard deviation 2267 and 659 ng/ml).
Conclusions:A sensitive and selective HPLC method for the determination of sorafenib in human serum was developed and also verified for peritoneal fluid. This method provides a useful tool for pharmacokinetic investigations as well as for therapeutic drug monitoring of sorafenib.
In this retrospective study, analyzing blood samples from daily clinical practice of patients in various clinical settings and with different indications for antifungal therapy, concomitant medication of lorazepam was associated with decreased posaconazole concentrations. Therefore, lorazepam but not temazepam might induce posaconazole clearance by glucuronidation.
In patients receiving 400 mg BID, the mean rate of serum levels >500 ng/mL in subsequent determinations was higher, if the first serum concentration during steady state was >300 ng/mL (mean 61.1%, median 60%, P = 0.002) or >500 ng/mL (67.7%, median 75%, P = 0.002). Based on this retrospective analysis, a posaconazole serum concentration >500 ng/mL at any time point might also help to predict sufficient drug concentrations.
Here we present 3 patients with abdominal pain, weight loss and fever in combination with abdominal tumours which were all attributable to an ongoing mycobacterial infection. Worldwide, but especially in developing countries, tuberculosis is still an important cause of morbidity and death. In industrialised countries, however, tuberculosis is rarely considered as a differential diagnosis, especially when the primary lesion is not localised in the lung. Primary abdominal manifestations, in particular, are a frequent cause of delayed diagnosis due to the often elaborated necessary diagnostics. Once the diagnosis has been established, a combination therapy starting with isoniazid, rifampicin, pyrazinamide and ethambutol, i. e., the standard therapeutic regimen for pulmonary tuberculosis, is recommended. Concomitant diseases and atypical courses, however, often constitute serious challenges to the treating physician. Therefore, we here give a review of the literature and discuss three cases of abdominal tuberculosis with regard to clinical characteristics, diagnostic pitfalls and courses of disease.
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