Leicester Royal Infirmary

About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.

Bioequivalence of two tablet formulations of capecitabine and exploration of age, gender, body surface area, and creatinine clearance as factors influencing systemic exposure in cancer patients

Abstract: Purpose: The objective of the study was to assess the bioequivalence of two tablet formulations of capecitabine and to explore the effect of age, gender, body surface area and creatinine clearance on the systemic exposure to capecitabine and its metabolites. Methods: The study was designed as an open, randomized two-way crossover trial. A single oral dose of 2000 mg capecitabine was administered on two separate days to 25 patients with solid tumors. On one day, the patients received four 500-mg tablets of formulation B (test formulation) and on the other day, four 500-mg tablets of formulation A (reference formulation). The washout period between the two administrations was between 2 and 8 days. After each administration, serial blood and urine samples were collected for up to 12 and 24 h, respectively. Unchanged capecitabine and its metabolites were determined in plasma using LC/MS-MS and in urine by NMRS. Results: Based on the primary pharmacokinetic parameter, AUC0–∞ of 5′-DFUR, equivalence was concluded for the two formulations, since the 90% confidence interval of the estimate of formulation B relative to formulation A of 97% to 107% was within the acceptance region 80% to 125%. There was no clinically significant difference between the tmax for the two formulations (median 2.1 versus 2.0 h). The estimate for Cmax was 111% for formulation B compared to formulation A and the 90% confidence interval of 95% to 136% was within the reference region 70% to 143%. Overall, these results suggest no relevant difference between the two formulations regarding the extent to which 5′-DFUR reached the systemic circulation and the rate at which 5′-DFUR appeared in the systemic circulation. The overall urinary excretions were 86.0% and 86.5% of the dose, respectively, and the proportion recovered as each metabolite was similar for the two formulations. The majority of the dose was excreted as FBAL (61.5% and 60.3%), all other chemical species making a minor contribution. Univariate and multivariate regression analysis to explore the influence of age, gender, body surface area and creatinine clearance on the log-transformed pharmacokinetic parameters AUC0–∞ and Cmax of capecitabine and its metabolites revealed no clinically significant effects. The only statistically significant results were obtained for AUC0–∞ and Cmax of intact drug and for Cmax of FBAL, which were higher in females than in males. Conclusion: The bioavailability of 5′-DFUR in the systemic circulation was practically identical after administration of the two tablet formulations. Therefore, the two formulations can be regarded as bioequivalent. The variables investigated (age, gender, body surface area, and creatinine clearance) had no clinically significant effect on the pharmacokinetics of capecitabine or its metabolites.

Effects of remifentanil and alfentanil on the cardiovascular responses to induction of anaesthesia and tracheal intubation in the elderly

Abstract: Background We compared the effects of remifentanil and alfentanil on arterial pressure and heart rate at induction of anaesthesia and tracheal intubation in 40 ASA I–III patients aged greater than 65 yr, in a randomized double-blind study. Methods Patients received either remifentanil 0.5 μg kg−1 over 30 s, followed by an infusion of 0.1 μg kg min−1 (group R) or alfentanil 10 μg kg−1 over 30 s, followed by an infusion of saline (group A). Anaesthesia was then induced with propofol, rocuronium, and 1% isoflurane with 66% nitrous oxide in oxygen. Results Systolic arterial pressure (SAP) and mean arterial pressure (MAP) decreased after the induction of anaesthesia (P Conclusions Remifentanil and alfentanil similarly attenuate the pressor response to laryngoscopy and intubation, but the incidence of hypotension confirms that both drugs should be used with caution in elderly patients.

No obvious advantages for thoracoscopic two-stage oesophagectomy.

Abstract: Thoracoscopically assisted Ivor-Lewis oesophagectomy potentially combines the pulmonary advantages of transhiatal oesophageal dissection, with the visibility and control permitted by thoracotomy This study reviewed 17 patients who underwent this procedure with an intrathoracic anastomosis Five patients required conversion to thoracotomy, four because of technical difficulties with the anastomosis After operation 13 patients had radiological evidence of atelectasis, six developed a left pleural effusion and five had clinically significant pneumonia Three patients developed an anastomotic leak, two of whom died giving an in-hospital mortality rate of 12 per cent Median postoperative hospital stay was 12 days Four patients developed benign anastomotic strictures requiring dilatation The 1- and 2-year survival rates were 73 per cent (11 of 15 patients) and 63 per cent (five of eight) respectively The use of minimal access techniques in this context does not appear to reduce the postoperative incidence of either pulmonary or anastomotic complications