Vancomycin (VCM), a glycopeptide antibiotic, was developed and released in the 1950's for the treatment of aerobic gram-positive infections and has been widely used mainly in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Early reports regarding the possibility of nephrotoxicity and ototoxicity led to concern about the use of VCM and monitor serum VCM concentrations.In general, the purposes of therapeutic drug monitoring (TDM) are to improve clinical effects, to avoid side effects, and to reduce drug costs. In the case of VCM, however, an exhaustive review of the literature revealed that there are no studies analyzing a direct effect of serum VCM concentrations and clinical outcome.1-3) There have been a few studies examining the minimum inhibitory concentration (MIC)/ minimum bactericidal concentration (MBC) ratios and cure rates, 4-6) these studies are not efficient to answer the question what concentration of VCM was required for the successful treatment of infections. Recently, some clinical reports evaluating the TDM of VCM have proposed the following conclusions: 1) TDM is associated with a decreased incidence of VCM-induced nephrotoxicity, indicating that TDM is a cost-effective procedure, 1,[7][8][9] and 2) VCM works most effectively if the concentration at the site of infection is maintained above MIC values throughout the dose interval. So, the clinical efficacy of VCM can usually be obtained if the trough concentration is sufficiently above the MIC at the site of infected organisms. 10,11) Since the MIC values for susceptible organisms were below 5 mg/ml and reported toxicities had occurred most often at drug serum concentrations above 40 mg/ml, clinicians and researchers designated therapeutic trough concentrations at 5-15 mg/ml and peak concentrations at 25-40 mg/ml. 1,[12][13][14] In practice, however, the peak concentration hardly exceeds 40 mg/ml, as long as the trough concentration is kept below 15 mg/ml. 15) For this reason, the policy of monitoring the trough concentration alone for VCM has recently spread worldwide. In Japan, however, both the trough and peak concentrations of VCM are monitored in most of hospitals. Therefore, it would be worthwhile to investigate whether monitoring peak concentration is essential or not.The purpose of the present study was to investigate the clinical utility of the TDM VCM and the relationship between its peak concentrations and clinical effects in MRSAinfected patients. MATERIALS AND METHODS Subjects and Study DesignSubjects (0-86 years of age) in this retrospective study were MRSA-infected patients who received intravenous infusion of VCM (Shionogi & Co., Ltd., Osaka, Japan) from January 1996 to March 2002 and also had confirmed the disappearance of the bacteria thereafter.The incidence of nephrotoxicity, including VCM-induced or MRSA-related nephrotoxicity, was compared between the TDM group (nϭ73) and the non-TDM group (nϭ111). Serum VCM concentrations in the TDM group were monitored within 10 d from the start of VCM ther...

A close relationship among postprandial hyperglycemia, advanced age, and hypercholesterolemia is a characteristic of SDM in patients with neurologic diseases. Therefore, monitoring the plasma glucose concentration 2 hours after lunch may be useful to detect SDM in these patients.

SUMMARYPurpose: To identify risk factors for hyperammonemia in pediatric patients with epilepsy. Methods: A total of 2,944 pediatric patients (ages 0-15 years) were classified into the following three groups: a group without drug treatment (n = 445, group I), a group receiving antiepileptic drugs other than valproic acid (VPA) (n = 673, group II), and a VPA-treated group (n = 1,826, group III). Hyperammonemia was defined as a plasma ammonia level exceeding 100 lg/dl with reference to the standard range and previous reports. Key Findings: The mean ammonia level of groups I, II, and III was 36.0, 56.0, and 86.8 lg/dl, respectively, and the incidence of hyperammonemia was 1.6%, 7.7%, and 31.7%, respectively. In each group, the mean ammonia level of patients aged 3 years or younger was significantly higher than that of patients aged 4-15 years. In group II, concomitant use of topiramate and zonisamide were risk factors for hyperammonemia (adjusted odds ratio [OR] 3.9, 95% confidence interval [CI] 1.7-9.2, and OR 3.5, 95% CI 1.9-6.5, respectively). In group III, the ammonia level increased in a VPA dose-dependent manner. At a VPA dose of 30 mg/kg, there was 4.3-fold increase in the incidence of hyperammonemia. The other significant risk factors identified were female gender (OR 1.3, 95% CI 1.0-1.6), symptomatic generalized epilepsy (OR 1.4, 95% CI 1.1-1.8), and the concomitant use of phenytoin (OR 4.7, 95% CI 3.3-6.9), phenobarbital (OR 2.2. 95% CI 1.6-3.2), acetazolamide (OR 6.6, 95% CI 2.5-17.2), topiramate, or zonisamide. Significance: A young age and concomitant use of carbonic anhydrase inhibitors are associated with an increased risk of hyperammonemia regardless of whether the patient is taking VPA. In patients receiving VPA, concomitant use of phenytoin and/or phenobarbital enhances the risk of hyperammonemia. An increase in ammonia can be caused by multiple factors. Our results may help clinicians to avoid problems of hyperammonemia. KEY WORDS: Hyperammonemia, Epilepsy, Children, Risk factor, Valproic acid, Phenytoin.Hyperammonemia is a frequent problem associated with antiepileptic drugs (AEDs) that can lead to vomiting, aggression, ataxia, and exacerbation of seizures. Acute hyperammonemia can also cause cerebral edema and severe brain damage (encephalopathy), whereas chronic hyperammonemia due to metabolic disorders is associated with developmental delay and intellectual disability (Cagnon & Braissant, 2007;Lichter-Konecki, 2008). Among the AEDs, valproic acid (VPA) is recommended as a first-line treatment for generalized epilepsy. Although VPA can cause an increase of the blood ammonia level, VPA therapy is rarely associated with hyperammonemic encephalopathy.The exact relationship between symptoms and the ammonia level remains unclear. Murphy and Marquardt (1982) reported that patients with hyperammonemia not exceeding 240 lg/dl were asymptomatic. In contrast, Coulter and Allen (1981) recommended reducing the VPA dose when the ammonia level exceeded 100 lg/dl. Our data (see later) indicate that hyperammo...

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There is a large interindividual variation in CD ratio of perampanel because its metabolism is highly susceptible to interactions with enzyme-inducing AEDs. Therapeutic drug monitoring could be clinically useful for determining the influence of AED CYP3A4 inducers on perampanel concentrations.