Chinese slimming capsules containing sibutramine sold over the internet: a case series.

Dtsch Arztebl Int. 2009 Mar; 106(13): 218-22Müller D, Weinmann W, Hermanns-Clausen MBACKGROUND: In recent years, the market for dietary supplements has grown. International products are readily available for purchase over the Internet. We report 17 cases of poisoning with a single product, said to be of purely herbal origin, that was bought over the Internet. A complete declaration of the ingredients was not available. METHODS: We performed a retrospective study of cases of poisoning documented by the Göttingen and Freiburg poison information centers from 2005 to 2008. In 4 cases, we were able to perform toxicological analyses of leftover capsules and urine samples. RESULTS: The manifestations of poisoning in the 17 documented cases included malaise, tachycardia, headache, agitation, arterial hypertension, nausea, vomiting, dyspnea, insomnia, left-sided chest pressure, elevated temperature, and, in two cases, psychosis after the substance was combined with atomoxetine and methylphenidate and with citalopram, olanzapine, and chlorprothixene. The frequency of cases rose markedly in the last year of the study. The toxicological analyses of all samples studied revealed sibutramine. The dose in each capsule was nearly twice the maximum daily dose sibutramine in the medication containing this substance that is licensed for use in Germany. CONCLUSIONS: Products available without a prescription whose contents are claimed to be purely herbal may nonetheless contain synthetic substances in concentrations far above the therapeutic range and may be a cause of poisoning. When taking the history of a patient possibly suffering from an intoxication, the physician should ask specifically about drugs, dietary supplements, and so-called lifestyle products that were obtained without a prescription. It would be desirable for the contents of all such products to be declared, as required by law, so that their suitability for the market can be checked.

Emerging significance of flavonoids as p-glycoprotein inhibitors in cancer chemotherapy.

J Pharm Pharm Sci. 2009; 12(1): 46-78Bansal T, Jaggi M, Khar R, Talegaonkar SChemotherapy forms the mainstay of cancer treatment particularly for patients who do not respond to local excision or radiation treatment. However, cancer treatment by drugs is seriously limited by P-glycoprotein (P-gp) associated multi-drug resistance (MDR) in various tumor cells. On the other hand, it is now widely recognized that P-gp also influences drug transport across various biological membranes. P-gp transporter is widely present in the luminal surface of enterocytes, biliary canalicular surface of hepatocytes, apical surface of proximal tubular cells of kidney, endothelial cells of blood brain barrier, etc. thus affecting absorption, distribution, metabolism and excretion of xenobiotics. Clinical significance of above mentioned carrier is appreciated from the fact that more than fifty percent of existing anti-cancer drugs undergo inhibitable and saturable P-gp mediated efflux. Consequently, there is an increasing trend to optimize pharmacokinetics, enhance antitumour activity and reduce systemic toxicity of existing anti-cancer drugs by inhibiting P-gp mediated transport. Although a wide variety of P-gp inhibitors have been discovered, research efforts are underway to identify the most appropriate one. Flavonoids (polyphenolic herbal constituents) form the third generation, non-pharmaceutical category of P-gp inhibitors. The effects produced by some of these components are found to be comparable to those of well-known P-gp inhibitors verapamil and cyclosporine. Identification of effective P-gp modulator among herbal compounds have an added advantage of being safe, thereby making them ideal candidates for bioavailability enhancement, tissue-penetration (e.g. blood brain barrier (BBB)), decreasing biliary excretion and multi-drug resistance modulating agents. The dual effects, i.e. P-gp modulation and antitumor activity, of these herbal derivatives may synergistically act in cancer chemotherapy. This paper presents an overview of the investigations on the feasibility and application of flavonoids as P-gp modulators for improved efficacy of anti-cancer drugs like taxanes, anthracyclines, epipodophyllotoxins, camptothecins and vinca alkaloids. The review also focuses on flavonoid-drug interactions as well as the reversal activity of flavonoids useful against MDR. In addition, the experimental models which could be used for investigation on P-gp mediated efflux are also discussed.