LC method for therapeutic drug monitoring of levetiracetam: Evaluation of the assay performance and validation of its application in the routine area

ObjectivesAn accurate and precise high-performance liquid chromatographic method using diode array detection for the determination of levetiracetam in human plasma has been developed and validated for use in pharmacokinetic studies.MethodsA harmonized validation strategy based on the accuracy profiles was used to select the most appropriate regression model and to determine the limits of quantitation as well as the concentration range of the developed analytical procedure. On the other hand, the present paper also shows this validation approach as a suitable tool to guaranty the quality of the results obtained by the use of the analytical validated methodology for plasma levetiracetam determination in a routine setting and to ensure the risk of obtaining the future measurements outside the previously fixed acceptance limits.ResultsAs pointed recently, the FDA, a weighted 1/x² quadratic regression model ranging from 0.53 to 107.00 mg/L was selected as the simplest calibration model that maximized the accuracy all over the range. Relative bias was < 5%, assay imprecision was always < 6% and mean extraction recovery from plasma was > 90%. So, accuracy did not exceed the acceptance limits settled at ± 20% according to the FDA or Washington conference regulatory requirements for bioanalytical methods. Internal quality control has been assessed over a 2 year time period. All controls were essentially found to provide levetiracetam concentrations within the target range according to the FDA.ConclusionsThe validated analytical procedure complies with strongest regulatory standards. The validated method has a sufficiently rapid turnaround time and their results are good enough to enable the laboratory to routinely provide useful and accurate pharmacokinetic data in time to adjust patient regimens.     

Gait epilepsy. A case report of gait-induced seizures

Reflex epilepsy includes a group of epileptic syndromes in which seizures are induced by a stimulus, either simple (visual, somatosensory, olfactory, auditory) or more complex (e.g., eating, thinking, reading). We document a case of reflex epilepsy in which focal seizures are triggered exclusively by gait. The patient is a young boy whose walking was impaired by abnormal motor phenomena on the left side. These phenomena were elicited by gait and were accompanied by a distinctive ictal pattern with centro-temporal discharges. After comparing this patient with others reported in the literature, we determined that he has an unusual type of reflex epilepsy for which we coined the term "gait epilepsy." This disorder must be considered when physicians are making a differential diagnosis in patients who have symptoms that suggest paroxysmal kinesigenic dystonia (PKD) or selective epileptic gait disorder.     

Morbid obesity treated by gastroplasty: radionuclide gastric emptying studies

Mechanisms by which gastroplasty for morbid obesity causes weight loss are poorly understood. We studied the role of altered gastric emptying in 50 patients before surgery, 1-4 weeks after surgery, and 2-24 months after surgery using technetium-99m pentetate in water for liquid meals and a Tc-99m styrene divinylbenzene copolymer resin in oatmeal for semisolid meals. We determined the emptying half-times of the stomach before and after surgery in the proximal and distal compartments. The proximal compartment emptied promptly in the early and late postoperative periods. The distal compartment emptied liquids at rates similar to those before surgery, while the late postoperative emptying of semisolids was significantly faster. The stoma connecting the two compartments thus permits rapid transit of liquids and semisolids without delay of distal compartment emptying. No correlation was seen between the emptying half-times or changes thereof and eventual weight loss. Delayed gastric emptying is therefore not the mechanism for satiety and weight loss after gastroplasty has been performed.     

A novel biweekly schedule with cisplatin and gemcitabine in advanced non-small cell lung cancer

A new schedule with cisplatin and gemcitabine administered biweekly was prospectively evaluated in stage IIIB or IV non-small cell lung cancer. We report the interim analysis of the safety and efficacy with the first 23 patients included. The mean age was 60. Thirteen patients (56.5%) were stage IIIB and 10 (43.5%) were stage IV The overall response rate was 47.8%: 69.2% for stage IIIB and 20% for stage IV The median survival among the 23 patients was 33 weeks and 1-year survival was 39%: 53.8% for stage IIIB and 20% for stage IV Seventy-seven cycles (154 administrations) were given. The mean number of cycles/patient was 3.3 (range: 1 to 6). Of the 154 administrations, 26 were delayed 1 week for recovery from toxicity. The dose intensity (Hryniuk criteria) was 94% of the planned dose. There was one toxic death with grade 4 thrombocytopenia and grade 4 esophagitis. In two patients, grade 3-4 vascular toxicity was observed, with distal arterial ischemic changes in the lower extremities. There were three (3.9%) episodes of grade 2 neutropenia, one (1.7%) of grade 3 and another one of grade 4. No cases of febrile neutropenia were seen. Predominant nonhematologic toxicities were asthenia and nausea/vomiting. This schedule of cisplatin and gemcitabine has a good therapeutic index and, as it is active, enrollment is ongoing to complete the second part of the study.     

Update on common indicators of nutritional status: food access, food consumption, and biochemical measures of iron and anemia

This paper presents some of the most commonly utilized indicators to assess food and nutritional status. With respect to the indicators reflecting food access, those addressing poverty as well as food consumption are included. In addition, a variety of serum biochemical measures for the estimation of iron nutritional status and anemia are discussed; it is recommended that some of these be adjusted to account for sex, age, physiological status, and altitude above sea level.     

Late-onset periodic asystolia during vagus nerve stimulation

Cardiac changes may occasionally occur during vagus nerve stimulation (VNS) used in epileptic patients. As they can be potentially life-threatening, it is important to detect them, and this is why an intraoperative test is performed during the implantation. Few cases of asystole during this test have been described. Only one patient with late-onset bradyarrythmia caused by VNS has been reported. This patient had been implanted 2 years and 4 months before the episode. We present another case of late asystole in a patient whose VNS had been implanted 9 years before the arrhythmia onset. In our patient, each run of stimulation produced bradyarrhythmias and very often severe asystolia due to atrium-ventricular block.