Dialysability of sugammadex and its complex with rocuronium in intensive care patients with severe renal impairment.

BACKGROUND: Renal excretion is the primary route for the elimination of sugammadex. We evaluated the dialysability of sugammadex and the sugammadex-rocuronium complex in patients with severe renal impairment in the intensive care unit (ICU). METHODS: Six patients in the ICU with acute severe renal impairment received general anaesthesia for transoesophageal echocardiography, to replace their tracheal tubes, or for bronchoscopy. Five of the six patients were in the ICU after cardiac/vascular surgery and one for pneumonia-induced respiratory failure. They all received rocuronium 0.6 mg kg(-1), followed 15 min later by sugammadex 4.0 mg kg(-1). Two patients were studied for two dialysis episodes and four patients for four episodes. Rocuronium and sugammadex concentrations were measured in plasma and dialysate at several time points before, during, and after high-flux dialysis. Dialysis clearance in plasma and dialysate, and reduction ratio (RR) (the extent of the plasma concentration reduction at the end of a dialysis episode when compared with before dialysis) were calculated for each dialysis episode. RESULTS: Dialysis episodes lasted on average 6 h. Observed RRs indicated mean reductions of 69% and 75% in the plasma concentrations of sugammadex and rocuronium, respectively, during the first dialysis episode. Reductions were around 50% during sequential dialysis episodes. On average, dialysis clearance of sugammadex and rocuronium in blood was 78 and 89 ml min(-1), respectively. CONCLUSIONS: Haemodialysis using a high-flux dialysis method is effective in removing sugammadex and the sugammadex-rocuronium complex in patients with severe renal impairment.

Long-term efficacy and safety of asenapine or olanzapine in patients with schizophrenia or schizoaffective disorder: an extension study.

INTRODUCTION: Safety and efficacy results, collected in schizophrenia and schizoaffective disorder patients treated for up to nearly 3 years, are presented for asenapine and olanzapine. RESULTS: Patients completing a 52-week randomized double-blind core study on flexible-dose asenapine (5 or 10 mg BID) or olanzapine (10 or 20 mg QD) could continue treatment until study blind was broken.290 patients on asenapine and 150 on olanzapine continued treatment for variable lengths of time [mean ± SD (range) 311.0 ± 146.1 (10 - 653) d and 327.4 ± 139.6 (15 - 631) d, respectively]. Adverse event (AE) incidence was lower during the extension (asenapine, 62%; olanzapine, 55%) than during the core study (78%, 80%). In both groups, body weight increase and incidence of extrapyramidal AEs were negligible during the extension. Mean PANSS total score changes during first year of treatment were - 37.0 for asenapine and - 35.3 for olanzapine, with further changes of 1.6 for asenapine and - 0.8 for olanzapine at the extension study endpoint. CONCLUSIONS: Clinical stability on asenapine as well as olanzapine was maintained, with few recurrent or newly emerging AEs beyond 1 year of treatment.

Metabolism of EICAR (5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide), a potent inhibitor of inosinate dehydrogenase.

The cytostatic agent 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR) causes a rapid and marked inhibition of inosinate (IMP) dehydrogenase activity in intact tumor cells. [3H]EICAR is metabolised in L1210 cells to its 5'-mono-, 5'-di- and 5'-triphosphate in a concentration-dependent manner. The metabolites accumulate proportionally with the initial extracellular EICAR concentrations (ranging from 0.25 to 200 microM). The nicotinamide adenine dinucleotide (NAD) analogue of EICAR, designated EAD, also accumulates within the cells and becomes the major metabolite after 48 hr incubation with 5 microM [3H]EICAR. EAD has a markedly longer intracellular half-life than EICAR 5'-mono-, 5'-di- and 5'-triphosphate. An additional EICAR metabolite elutes on an anion exchange Partisphere SAX HPLC chromatogram between EICAR 5'-di- and 5'-triphosphate. Its intracellular levels are approximately 10-fold lower than those of EAD and the nature of this metabolite has still to be identified. The differential role of EAD and EICAR 5'-monophosphate in the inhibition of IMP dehydrogenase is currently under investigation.

Human teratocarcinoma cells express functional insulin-like growth factor I receptors.

Using iodinated insulin-like growth factors (IGFs) we have detected receptors for IGF-I at the cell surface of the clonally derived human embryonal carcinoma cell line Tera 2 clone 13. Affinity crosslinking of IGFs to Tera 2 clone 13-derived membrane preparations revealed the presence of proteins with features of both type-I and type-II IGF receptors. Treatment of Tera 2 clone 13 cells with retinoic acid to induce differentiation results in an increased number of cell surface receptors, apparently without altering the ratio of type-I and type-II receptors. In addition, Tera 2 clone 13 IGF-I receptors catalyze (auto)phosphorylation at tyrosine upon IGF-I and insulin binding. These findings suggest that type-I IGF receptors might be involved in mediating the effects of IGFs and insulin upon the proliferation of Tera 2 clone 13 cells.