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Hydrocephalus is usually resolved by diverting cerebrospinal fluid through a surgically implanted intra-ventricular catheter (shunt). The aim of this study was to characterize vancomycin pharmacokinetic (PK) parameters and optimal dosage in shunted patients under vancomycin treatment. Intensive Care and Neurosurgical Units. University Hospital. Retrospective data of vancomycin blood concentrations, demographics and biochemical parameters, from a Therapeutic Drug Monitoring (TDM) program, in ventricle-external shunted patients (Group A) and controls (Group B) were collected. In all subjects, several blood samples at steady state conditions were drawn. Individual PK parameters such as drug clearance (CL) and volume of distribution (V) were estimated by using an one-compartmental PK model and later, dosage regimens were individually adjusted by Bayesian analysis. The obtained CL and V mean ± standard deviation were compared between both groups (A versus B). Vancomycin dosage regimens between both groups were also compared. Patients demographics, clinical records, creatinine clearance by Cockcroft-Gault, vancomycin blood levels, vancomycin pK parameters and optimal initial IV vancomycin dosage. Forty-five patients were included in the study: 15 patients in group A and 30 subjects in group B. Significant differences between CLA and CLB means were observed, while not between VA and VB. In shunted patients, the required vancomycin daily dose to reach target concentrations was significantly higher than the dose needed in the control group (49.25 ± 12.28 mg/kg/day vs. 31.74 ± 6.70 mg/kg/day; P < 0.0005). Greater vancomycin clearance was found in our shunted patients, thus they required higher vancomycin daily doses compared to the control group. Consequently, vancomycin TDM in shunted patients should be advisable in order to guarantee antibiotic blood concentrations within the recommended therapeutic range.

A colorimetric method for the assay of carbidopa and methyldopa either in pure form or in pharmaceutical preparations is described. The method is based on the reduction of tetrazolium blue chloride in a non-aqueous alkaline medium by the substances analysed, and the measurement of the absorbance of the pink-coloured diformazan solution, which is caused by this reduction. The spectra of the aforesaid solutions exhibit an absorption maximum atλ= 525 nm. The apparent molar absorptivities and Sandell's sensitivities (in 1·mol−1 ·cm−1 and ng· cm−2, respectively) are 1.2·105 and 1.9 for carbidopa and 7.07· 104 and 3.0 for methyldopa. The solution of diformazan formed obeys Beer's law in the concentration range of 0.05–4.0 ppm for carbidopa and 0.1–6.0 ppm for methyldopa. The slope and intercept of the corresponding regression line equation were obtained with a correlation coefficient of 0.9999 for carbidopa and 0.9994 for methyldopa. The variables affecting the development of the colour are investigated and the conditions are optimized. Compared with other procedures this method showed to be more simple and rapid, highly sensitive, precise and accurate. Results obtained by application of the proposed method and the official one, were in good agreement, while statistical comparison by the Student's t-test shows no significant difference between the two sets of the results.

With the licensing of new antiepileptic drugs there is an obvious need for the determination of the comparative efficacy, tolerability and overall effectiveness against standard (existing) antiepileptic drugs. Such data can only be determined within the context of well‐designed randomised clinical trials (RCTs). Such comparative monotherapy studies may form a part of phase III drug development programmes for a new antiepileptic drug. They may be commenced once there is satisfactory evidence for efficacy and safety derived from placebo‐controlled add‐on studies in more refractory populations of patients. In this manuscript definitions of outcomes such as effectiveness, efficacy, and tolerability are given. Health‐related quality of life measures are presented, and it can be argued that such measures should be a primary outcome variable. However, there is little evidence that any quality of life measures have sufficient validity and sensitivity to be a useful tool in the comparison of drug treatments for epilepsy. Different populations can be studied in ‘withdrawal to monotherapy’ designs. In such studies patients poorly controlled on their existing therapy are randomised to receive different monotherapy regimes with withdrawal of their existing antiepileptic drugs. This clinical trial design has not been used in genuine comparisons between antiepileptic drugs and the efficiency of this approach has yet to be determined. Experience from studies comparing monotherapy would suggest that differences in efficacy between antiepileptic drugs in the target populations may be difficult to detect. Differences likely exist between the incidence and profile of adverse effects between different drugs. The main benefit of new antiepileptic drugs may be in reducing the incidence and severity of adverse reactions compared to older drugs and in doing so they may prove to be more effective.

The stability of diamorphine (0.02 mg/ml as the hydrochloride) in 250 ml bupivacaine hydrochloride (0.15% wt/vol infusion) was studied by high pressure liquid chromatography at temperatures in the range 7 to 45°C. Diamorphine hydrochloride was degraded by approximately 0.13% per day at 7°C. No bupivacaine hydrochloride degradation was detectable during the study. The storage life of the combination at 7°C, based on the lower 95% confidence limit of the time to 5% diamorphine hydrochloride degradation, was 14 days. The stability at 25°C was adequate to allow transport and administration over 24 h at ambient temperature. Stability was also maintained for at least 24 h at 32 and 45°C. Infusion of the mixture with an ambulatory infusion pump which uses a standard polyvinyl chloride infusion bag is therefore possible. A study of its compatibility with different infusion pump medication reservoirs was not undertaken. The drugs were also stable on frozen storage at −18°C for up to 6 months.