Pharmacokinetic modelling of valproic acid from routine clinical data in Egyptian epileptic patients

OBJECTIVE: This paper describes a developed pharmacokinetic model for the estimation of valproic acid (VPA) clearance (CL) calculated from routine clinical data taken from Egyptian epileptic patients. METHODS: Retrospective clinical data from 81 adult and paediatric epileptic patients with one trough VPA serum concentration per patient were analysed using NONMEM to estimate drug CL and determine the influence of different covariates. A qualification group of 20 epileptic children (3-13 years old) was used to evaluate the final model. RESULTS: The population CL as estimated by base model (no covariates) was 0.581 l h(-1) with inter-individual variability (C.V. %) of 17.4% and SD of residual error was 6.82 mg l(-1). Univariate selection and backward deletion of different covariates led to the development of the final regression model of CL as follows: CL(Lh-1) = 0.101 + 0.151 * CBZ + 0.000248 * VPADD + 0.0968 * age/20 + 0.0803 * INDI, in which CBZ indicates co-administration of carbamazepine, VPADD the daily dose of VPA and INDI uncontrolled epilepsy. The between-subject variability in CL was 23.6% while the standard deviation of the residual error was 5.24 mg l(-1). The model predictions in the qualification group were found to have no bias and satisfactory precision. CONCLUSION: The population pharmacokinetic model for VPA could be used for a priori recommendation and dose optimisation of that drug in the Egyptian population of epileptic patients.     

Conformational perturbations in retro-analogs of the tBuCO-Ala-Gly-NHiPr dipeptide Crystal structure of the retro-dipeptide with a reversed Ala-Gly amide bond

The three retro-analogs of the tBuCO-Ala-Gly-NHiPr dipeptide, in which each amide bond had been successively reversed, were studied in solution by ¹H-n.m.r. and i.r. spectroscopy with reference to the conformational properties of their parent dipeptide. Reversal of the Ala-Gly amide bond proved to perturb the folding tendency of the backbone less than the inversion of either of the terminal amide bonds. The crystal structure of the retro-peptide containing a reversed Ala-Gly amide bond was also solved by X-ray diffraction and constitutes the first available data for this retro-peptide series. In contrast to the βII-folded structure of the parent dipeptide, the retro-peptide molecule adopts an open conformation in the crystal.     

Bone mineral assessment: new dual-energy CT approach

Most clinical quantitative computed tomographic (CT) determinations of bone mineral content are hampered by inability to properly account for the various substances contained within the spongiosa (spongy bone). In general, the presence of adipose tissue lowers the CT numbers (Hounsfield units) and leads to underestimation of bone mineral content. Collagen matrix has the opposite effect. A new approach to obtaining data from postreconstruction dual-energy CT scans accounts for five principal constituents of the spongiosa. In addition to bone mineral values, the method also provides the adipose tissue concentration, calcium content, and density of the total trabecular space. Since calcium values are provided, the measurements can be compared with prereconstruction dual-energy data that are acquired simultaneously. A new solid-plastic calibration phantom was utilized in this study, and data were obtained from 26 subjects. Dual-energy data were correlated with single-energy measurements (r greater than .96), and calcium measurements were correlated with the bone mineral determinations (r = .97) in these 26 cases. All measurements of the various vertebral constituents agreed with published values.     

Hepatitis C virus infection in chronic liver disease and hepatocellular carcinoma in Saudi Arabia

The prevalence of antibody to hepatitis C virus (HCV) was determined in 139 patients with chronic liver disease (CLD) and 42 patients with hepatocellular carcinoma (HCC) during one year at the Riyadh Military Hospital, Saudi Arabia. The anti-HCV was detected in 36 of 96 (37.5%) HBsAg-negative patients with chronic liver disease and six of 43 (13.9%) HBsAg-positive patients with chronic liver disease. In addition, 11 (42.3%) HBsAg-negative hepatocellular carcinoma patients and two of 16 (12.5%) HBsAg-positive hepatocellular patients had antibody to HCV. The anti-HCV prevalence was 1.5% in 4818 healthy blood donors and 1% in 385 antenatal patients. The overall HCV seropositivity of 30.4% in 181 liver disease patients (CLD and HCC) in Saudi Arabia is lower than that reported from European countries.     

中药对过敏性紫癜肾炎患儿血浆内皮素和免疫功能的影响

用中药加雷公藤治疗过敏性紫癜肾炎患儿23例，观察其急性期、缓解期的血浆内皮素和免疫功能，并与单纯应用雷公藤的15例比较，结果中药加雷公藤组缓解或血浆内皮素和IGG、IGA均明显低于雷公藤组；T3细胞明显高于雷公藤组；T4/T8比值明显低于雷公藤组。提示中药加用雷公藤比单独使用雷公藤治疗过敏性紫问肾炎更有利于患儿血浆内皮素水平和免疫功能的恢复。