Current Pharmaceutical Biotechnology - Volume 12, Issue 2, 2011

Aim of the study: To assess tramadol and O-desmethyltramadol (M1) concentrations and their correlations with analgesia in patients with cancer pain. Patients and methods: Thirty opioid - naive patients with nociceptive pain intensity on VAS (visual analogue scale) > 40 received controlled-release tramadol as the first (15 patients, 7 days) or as the second opioid (15 patients, 7 days). Blood samples were taken on day 2, 4 and 7 at each study period. Tramadol and M1 were assayed by HPLC method. Results: During the first week a trend (p = 0.067) of tramadol level increase was observed in the third comparing to the first assay. In the second week a significant increase of tramadol concentration was observed in the second (p < 0.001) and in the third (p < 0.001) in comparison to the first assay. No significant changes in M1 concentrations were found in the first week. A significant increase of M1 concentration was noted in the second (p < 0.001) and in the third (p < 0.001) assays comparing to the first M1 determination in the second week. Conclusions: A relatively stable tramadol and M1 levels in the first week could be caused by intense tramadol dose titration in the first two days to achieve effective analgesia. The same pattern of tramadol and M1 level increase in the second week indicate their contribution to tramadol analgesia. Few significant correlations were found between tramadol dose, tramadol and M1 serum concentrations with analgesia suggesting the need of individual tramadol dose titration.

Local anesthetic toxicity is a rare, but potentially lethal, complication of regional anesthesia that cannot be prevented by any single measure. It is associated with CNS excitation and can lead to refractory cardiac dysfunction and collapse. The development of lipid emulsion for the treatment of anesthetic-induced toxicity resulted from a set of observations during a study on the potent, lipophilic drug bupivacaine and its associated clinical risk of intransigent cardiac toxicity in otherwise healthy individuals. Subsequent laboratory studies and clinical reports have shown that infusion of lipid can reliably reverse toxicity from potent local anesthetics as well as other drugs. The underlying mechanisms of lipid resuscitation may be a combination of a ‘lipid sink’ and metabolic effect. Lipid rescue has led to a reduction in fatalities associated with severe systemic toxicity, but continued research is necessary for a better mechanistic understanding. Increased physician awareness and education, as well as optimized treatment protocols, will significantly reduce the rate of morbidity and mortality from local anesthetic toxicity.

An early and reliable assessment of therapeutic efficacy during the treatment of cancer is essential to achieve an optimal treatment regimen and patient outcome. The use of labeled peptides to monitor tumor response is associated with several advantages. For example, peptides are very stable, non-immunogenic, are easy to label for imaging, they undergo rapid clearance from the circulation, can penetrate tumor tissue, and are inexpensive to synthesize. In this review, studies using recombinant and non-recombinant peptides to monitor the response of glioblastoma multiforme, lung, breast, pancreas, colon, prostate, and skin carcinomas to radiation and/or chemotherapeutics such as camptothecin, doxorubicin, etoposide, 5-fluorouracil, paclitaxel, AG3340, sunitinib, and dasatinib, are presented. A consideration of the imaging techniques available to monitor peptide localization, including near-infrared (NIR) fluorescence, magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasonography, is also included. Peptides that have been successfully used to monitor various tumor types and therapies have been shown to target proteins that undergo changes in expression in response to treatment, endothelial cells that respond to radiation, or mediators of apoptosis. Peptides that are able to selectively bind responsive versus unresponsive tumors have also been identified. Therefore, the advantages associated with the use of peptides, combined with the capacity for selected peptides to assess tumor response as demonstrated in various studies, support the use of labeled peptides to evaluate the effectiveness of a given cancer therapy.