Pharmacokinetics of Fosphenytoin in Patients with Hepatic or Renal Disease

PURPOSE: The pharmacokinetic behavior of fosphenytoin (FOS), the water-soluble prodrug of phenytoin (PHT), has been characterized in normal subjects. This is the first study of the effect of hepatic or renal disease on the rate and extent of conversion of FOS to PHT. METHODS: A single dose of fosphenytoin (250 mg over a period of 30 min) was administered to subjects with hepatic cirrhosis (n = 4), renal disease requiring maintenance hemodialysis (n = 4), and healthy controls (n = 4). Serial plasma concentrations were measured, and pharmacokinetic parameters were calculated. RESULTS: The mean time to reach the peak plasma FOS concentration was similar for each of the three groups. However, the mean time to achieve peak plasma concentrations of PHT tended to occur earlier in the hepatic or renal disease groups than in healthy subjects. The half-life of FOS was 4.5, 9.2, and 9.5 min for the three groups, respectively. There was a trend toward increased FOS clearance and earlier peak PHT concentration in subjects with hepatic or renal disease. This finding is consistent with decreased binding of FOS to plasma proteins and increased fraction of unbound FOS resulting from decreased plasma protein concentrations associated with these disease states. The conversion of FOS to PHT was equally efficient in subjects with hepatic or renal disease and healthy subjects. CONCLUSIONS: Although the differences in pharmacokinetic parameters between the three groups were not statistically significant, these data suggest the need for close clinical monitoring during FOS administration to patients with hepatic or renal disease. To minimize the incidence of adverse effects in this patient population, FOS may need to be administered at lower doses or infused more slowly.     

Threshold point utilisation in juror decision-making

This study aims to identify whether a model of juror decision-making (i.e. the threshold point model) that encompasses both rational and intuitive decision-making exists. A total of 60 participants were selected who are eligible for jury duty in Scotland. These individuals read nine vignettes and rated the evidence of each vignette separately by placing the evidence in either a guilty, a not guilty or a not proven (a verdict type specific to Scotland) counter. Participants were asked after being presented with each piece of information to state how likely they thought the suspect was of being guilty, on a scale from 1 to 100. The data are best described using a flexible model (i.e. a diffusion model) that allows for information integration. Future research should examine whether or not the diffusion model can explain cognitive fallacies, such as confirmation bias, that are commonly studied in decision science.     

Diabetes prevalence is associated with obesity,hypertension, dyslipidemia,and sociodemographic factors in adults living in Casablanca-Settat and Rabat-Sale-Kenitra regions,Morocco

International Journal of Diabetes in Developing Countries - Diabetes is increasing at an alarming rate worldwide, but little is known about its risk factors in Morocco. This study aimed to...     

高血压治疗的现代途径(MATH)

标　　题　硝苯地平胃肠治疗系统对老年患者的抗高血压治疗作用作　　者　ＢｒａｖｏＥＬ,ＫｒａｋｏｆｆＬＲ,ＴｕｃｋＭＬ,ｅｔａｌ.　　参考文献　ＡｍＪＨｙｐｅｒｔｅｎｓ,1990,3:326Ｓ目　　的　评估硝苯地平的新剂型胃肠治疗系统ＧＩＴＳ治疗高血压的疗效和安全性。研究疾病　高血压病。设　　计　多中心、开放性临床研究。病人资料　1155例ＤＢＰ在95～110ｍｍＨｇ的高血压患者。随　　访　至目标血压达到后12周。治疗方案　硝苯地平控释片30ｍｇ/ｄ,在6周内剂量逐渐增至最大量180ｍｇ/ｄ,每次增量为30ｍｇ,目标血压为舒张压降至90…     

CA19‐9 as a predictor of tumor response and survival in patients with advanced pancreatic cancer treated with gemcitabine based chemotherapy

Aims: The aim of this study was to determine the predictive role of pretreatment carbohydrate antigen 19‐9 (CA19‐9) measurement and its change after one cycle of gemcitabine‐based therapy for response, time to progression (TTP) and overall survival (OS). Methods: Analyses were derived from three consecutive gemcitabine‐containing phase II clinical trials between 1997 and 2004. Results: A total of 111 patients with pancreas cancer was studied. Baseline CA19‐9 concentrations were dichotomized near the median. Lower baseline CA19‐9 levels were positively associated with OS (median 9.1 vs 6.1 months, P = 0.0057) and TTP (median 6.4 vs 4.2 months, P = 0.0044).The covariate adjusted hazard ratio (HR) for progression among patients with baseline CA19‐9 ≥ 1000 ng/mL was HR = 1.94 (95% CI 1.24–3.02), with P = 0.0035. The covariate adjusted risk of death among patients with baseline CA19‐9 ≥ 1000 ng/ml was similarly elevated: HR = 1.90 (95% CI 1.23–2.94), with P = 0.0039. Change in CA19‐9 levels from baseline to the end of treatment cycle 1 did not predict objective response (P = 0.75). There was somewhat longer OS (median 8.7 vs 7.1 months) and TTP (median 7.1 vs 5.4 months) in patients with ≥50% reduction in serum CA19‐9 concentrations, but this was not statistically significant (P = 0.74 and 0.81, respectively). Conclusion: Baseline CA19‐9 levels may predict survival in patients with advanced pancreas cancer. The change in CA19‐9 levels determined within 1 month of the initiation of therapy did not predict treatment outcome.