The impact of a nutritional intervention based on egg white for phosphorus control in hemodialyis patients.

BACKGROUND AND AIMS: Here we describe a dietary intervention for hyperphosphatemia in dialysis patients based on the partial replacement of meat and fish, which are one of the main sources of alimentary phosphorous, with egg white, a virtually phosphorous-free protein source. This intervention aims to reduce phosphorous intake without causing protein wasting. PATIENTS AND METHODS: As many as 23 hyperphosphatemic patients (15 male and 8 female, mean age 53.0 ± 10.0 years) on chronic standard 4 h, three times weekly, bicarbonate hemodialysis were enrolled in this open-label, randomized controlled trial. Patients in the intervention group were instructed to replace fish or meat with egg white in three meals a week for three months whereas diet was unchanged in the control group. RESULTS: Serum phosphate concentrations were significantly lower in the intervention group than in controls after three (4.9 ± 1.0 vs 6.6 ± 0.8; p < 0.001) but not after one month of treatment. Phosphate concentrations decreased more from baseline in the intervention than in the control group both after one (-1,2 ± 1,1 vs 0,5 ± 1,1; p = 0.004) and after three (-1,7 ± 1,1 vs -0,6 ± 1,1; p < 0.001) months of follow-up. No change either in body weight or in body composition assessed with bioelectrical impedance analysis or in serum albumin concentration was observed in either group. CONCLUSION: The partial replacement of meat and fish with egg white induces a significant decrease in serum phosphate without causing protein malnutrition and could represent a useful instrument to control serum phosphate levels in hemodialysis patients. CLINICALTRIALS. GOV IDENTIFIER: NCT03236701.

Short-Term Changes in Body Composition and Response to Micronutrient Supplementation After Laparoscopic Sleeve Gastrectomy.

BACKGROUND: We evaluated dietary intakes, body composition, micronutrient deficiency, and response to micronutrient supplementation in 47 patients before and for 6 months after laparoscopic sleeve gastrectomy (LSG). METHODS: Before, 3, and 6 months after LSG, we measured dietary intakes with food-frequency questionnaires, body composition with bioimpedance analysis (BIA) and bioelectrical vector analysis (BIVA), and plasma concentrations of iron, Zn, water-, and lipo-soluble vitamins. RESULTS: After LSG, energy intake significantly decreased and patients lost weight, fat mass, and free-fat mass. BIVA showed a substantial loss of soft tissue body cell mass (BCM) with no change in hydration. Before surgery, 15 % of patients were iron deficient, 30 % had low levels of zinc and/or water-soluble vitamins, and 32 % of vitamin 25(OH)-D3. We treated iron deficiency with ferrous sulfate, isolated folate deficiency with N5-methyiltetrahydrofolate-Ca-pentahydrate, and deficiencies in vitamin B1, B12, or Zn, with or without concomitant folate deficiency, with multivitamin. No supplementation was given to vitamin 25(OH)-D3 deficient patients. At first follow-up, 7 % of patients developed new deficiencies in iron, 7 % in folic acid (n = 3), and 36 % in water-soluble vitamins and/or zinc whereas no new deficit in vitamin 25(OH)-D3 occurred. At final follow-up, deficiencies were corrected in all patients treated with either iron or folate but only in 32 % of those receiving multivitamin. Vitamin 25(OH)-D3 deficiency was corrected in 73 % of patients even though these patients were not supplemented. CONCLUSION: LSG-induced weight loss is accompanied by a decrease in BCM with no body fluid alterations. Deficiencies in water-soluble vitamins and Zn respond poorly to multivitamin supplementation.

Effect of short-term synbiotic treatment on plasma p-cresol levels in patients with chronic renal failure: a randomized clinical trial.

BACKGROUND AND AIMS: In patients with chronic kidney disease (CKD), alterations in gut microbiome are posited to be responsible for gastrointestinal symptoms and generation of p-cresol, a uremic toxin that has been associated with CKD progression and cardiovascular mortality. This pilot study investigated whether Probinul-neutro®, a synbiotic that normalizes intestinal microflora, may lower plasma p-cresol concentrations and reduce gastrointestinal symptoms in non-dialyzed CKD patients. METHODS AND RESULTS: This was a double-blind, randomized placebo-controlled trial. Thirty patients on 3-4 CKD stages were randomized to receive either Probinul neutro® or placebo for 4 weeks. Total plasma p-cresol concentration was assessed at baseline, and 15 and 30 days after treatment start. At the same study times, ease and frequency of defecation, upper and lower abdominal pain, stool shape, borborygmi, and flatus were quantified by subjective assessment questionnaires. Compared to baseline total plasma p-cresol median concentrations on 15th and 30th day were significantly lower in patients receiving Probinul-neutro® (2.31 and 0.78 vs. 3.05 µg/ml, p < 0.05; n = 18); no changes of plasma p-cresol concentrations were recorded in placebo-treated patients. No significant changes in gastrointestinal symptoms were observed during the study both in Probinul-neutro®-treated and placebo-treated patients. CONCLUSION: Probinul-neutro® lowered total plasma p-cresol concentrations but did not ameliorate gastrointestinal symptoms in non-dialyzed CKD patients. Because high plasma concentrations of p-cresol in early phases of CKD are predictive of progression to end-stage renal disease, the results of our study suggest that synbiotics deserve attention as possible tools to delay CKD progression towards end-stage renal disease (ESRD). CLINICALTRIALSGOV IDENTIFIER: NCT02008331.

Dietary phosphate restriction in dialysis patients: a new approach for the treatment of hyperphosphataemia.

BACKGROUND AND AIM: Elevated serum phosphate and calcium-phosphate levels play an important role in the pathogenesis of vascular calcifications in uraemic patients and appear to be associated with increased cardiovascular mortality. We aimed to evaluate the effects of a partial replacement of food protein with a low-phosphorus and low-potassium whey protein concentrate on phosphate levels of dialysis patients with hyperphosphataemia. METHODS AND RESULTS: Twenty-seven patients undergoing chronic haemodialysis were studied for a 3-month period. In the intervention group (n = 15), food protein were replaced by 30 or 40 g of low-phosphorus and low-potassium protein concentrate aimed at limiting the phosphate intake. In the control group (n = 12) no changes were made to their usual diet. Anthropometric measurements, biochemical markers and dietary interviews were registered at baseline and during the follow-up period. From baseline to the end of the study, in the intervention group, serum phosphate and circulating intact parathyroid hormone levels lessened significantly (8.3 ± 1.2 mg/dL vs 5.7 ± 1.4 mg/dL and 488 ± 205 pg/ml vs 177 ± 100 pg/ml respectively; p < 0.05) with decreasing of phosphate and potassium intake. No significant differences were found in the control group. No significant changes were observed in serum albumin, calcium, potassium, Kt/V, body weight and body composition in both the intervention and control groups. CONCLUSION: Dietary intake of phosphate mainly comes from protein sources, so dietary phosphorus restriction may lead to a protein/energy malnutrition in a dialysis patient. A phosphorus-controlled diet plan including a nutritional substitute resulted in serum phosphate and intact parathyroid hormone decrease without nutritional status modifications in dialysis patients.

The impact of obesity on skin disease and epidermal permeability barrier status.

BACKGROUND: Obese subjects frequently show skin diseases. However, less attention has been paid to the impact of obesity on skin disorders until now. OBJECTIVE: The purposes of this study are: to highlight the incidence of some dermatoses in obese subjects and to study the water barrier function of the obese skin using transepidermal water loss (TEWL). METHODS: Sixty obese subjects and 20 normal weight volunteers were recruited. Obese group was further divided into three body mass index (BMI) classes: class I (BMI 30-34.9 kg/m(2)), class II (BMI 35-39.9 kg/m(2)) and class III (BMI 40 g/m(2)). All subjects attended dermatological examination for skin diseases. To assess barrier function, TEWL measurements were performed on the volar surface of the forearm using a tewameter. RESULTS: The results of this study showed that: (i) obese subjects show a higher incidence of some dermatoses compared with normal-weight controls; in addition the dermatoses are more, frequent as BMI increases; (ii) the rate of TEWL is lower in obese subjects, than in the normal-weight subjects, particularly in patients with intra-abdominal obesity. CONCLUSION: Specific dermatoses as skin tags, striae distensae and plantar hyperkeratosis, could be considered as a cutaneous stigma of severe obesity. The low permeability of the skin to evaporative water loss is observed in obese subjects compared with normal weight control. Although the physiological mechanisms are still unknown, this finding has not been previously described and we believe that this may constitute a new field in the research on obesity.

Body mass index and skinfold thickness versus bioimpedance analysis: fat mass prediction in children.

Childhood obesity increases the risk of morbidity whether or not obesity persists into adulthood. Measurement of body fat content using bioimpedance analysis (BIA) is a useful tool in epidemiologic studies. Both tricep skinfold thickness (TST, mm) and body mass index (BMI, kg/m(2)) are indirect, simple methods and easy to perform for assessing body composition. These methods are generally accepted as good clinical measures for defining childhood obesity. The aim of our study was to evaluate fat mass (FM, kg and %) measurements using TST and BIA (50 kHz) in a cohort of 6-year-old Italian children. A total of 228 southern Italian children (121 boys, 107 girls), randomly selected in nine local primary schools, were included in the study. The correlation between methods for measuring FM was calculated. Linear regression analysis showed a significant positive correlation between FM measured with BIA and BMI ( r=0.92, p<0.001) and with TST ( r=0.79, p<0.001). We conclude that FM measurement using TST and BIA is comparable in different BMI ranges. However, BIA is a useful and alternative method for detecting body composition in children and may be a more precise tool than TST for measuring FM in epidemiological studies in pediatric populations.

Impedance vector distribution by body mass index and conventional bioelectrical impedance analysis in obese women.

BACKGROUND AND AIM: To compare the body fluid status assessments provided by conventional bioelectrical impedance analysis (BIA) and vector BIA in moderate and severe obesity. METHODS AND RESULTS: We studied 516 normotensive Caucasian women (mean age: 48 +/- 9.2 years), who were age-matched and divided into four groups on the basis of their body mass index (BMI): 99 normal weight women with a BMI of 19-25 Kg/m2; 228 preobese overweight women with a BMI of 25-30 Kg/m2; 132 women with class I-II obesity (BMI: 30-35 Kg/m2), and 57 women with class III obesity (BMI: 40-64 Kg/m2). Single-frequency (50 kHz) tetrapolar (hand-foot) bioelectrical impedance measurements were made, and total body water (TBW) and extracellular water (ECW) were estimated using conventional BIA regression equations. The RXc graph method was used for vector BIA, with the set of 327 women with a BMI of 19-30 Kg/m2 being adopted as the reference population. Mean vector displacement followed a definite pattern, with progressive vector shortening as the BMI increased, and along a fixed phase angle. This pattern indicates more TBW due to a greater soft tissue mass with average normal hydration. Short and downsloping vectors indicating fluid overload were more frequent in the group with class III obesity than in the group with class I obesity (19 vs 5%). The absolute values of TBW and ECW were significantly higher in the obese and overweight subjects than in those with normal weight subjects. TBW as a percentage of body weight was significantly lower in the obese subjects. CONCLUSIONS: BMI influenced the impedance vector distribution pattern, which proved to be consistent up to a BMI of 64 Kg/m2. Obese women with an altered body composition can be identified and monitored using vector BIA.

Nutritional intervention in a hemodialysis pregnant woman: a case report.

Pregnancy in dialysis patients is a rare occurrence. When pregnancy does occur, the risk of spontaneous abortion, stillbirth and neonatal complications, such as prematurity and growth retardation, are fairly high. The authors describe their experience in the follow-up of a patient with chronic renal failure who became pregnant during regular dialysis treatment and followed nutritional care. The outcomes were successful and she gave birth to a healthy baby. It is emphasized that special dedication to the nutritional control enabled a good outcome of the pregnancy. The importance of the nutritionist intervention in the follow-up of dialysis patients with the integration of a multidisciplinary staff is stressed.

[Predictive and diagnostic factors of malnutrition in hemodialysis patients]. / Fattori predittivi e diagnostici della malnutrizione nel paziente in trattamento emodialitico.

The relationship between malnutrition and inflammation is by now well established. IL-6 and, probably, other proinflammatory cytokines (mainly IL-1 and TNF) may represent the link between these two entities since these interleukins may promote loss of appetite, muscle protein breakdown and reduced hepatic synthesis of "negative" acute phase proteins like albumin, prealbumin and transferrin. IL-6 also stimulates up to 1000 fold the hepatic synthesis of "positive" acute phase proteins, mainly C-reactive Protein (CRP) and Serum Amyloid A. The association between CRP and cardiovascular mortality in the general population, as well as in haemodialysed uraemic patients, is well established. These crucial interrelationships have modified the interpretation of serum albumin concentration in the diagnosis of malnutrition; a reduced serum albumin concentration, in fact, in the presence of high CRP values should point towards a diagnosis of inflammation, though the inflammation may often induce weight loss or a condition of malnutrition. After switching most patients to a more biocompatible dialysis membrane and improvement of the quality of the dialysis fluid (by adopting hydrophobic filters at the water entry of dialysis devices and bicarbonate powder cartridges) nephrologists have focused their attention on other sources of inflammation (e.g. artificial vascular protheses, presence of infected thrombi, Clamidiae, Helicobacter Pilori, dental granulomas etc.). Starting from these assumptions the diagnosis of malnutrition, once focused mainly on serum albumin reduction, must be based on other parameters (clinical history of body mass wasting, dietary and anthropometric assessment, subjective global assessment, bioimpedance analysis etc.). All these investigations, however, must be examined together to obtain suitable information on the risk of malnutrition in dialysis patients. A comprehensive approach to malnutrition-inflammation in dialysis patients is the object of the present nephrology conference.

Abnormalities of bioimpedance measures in overweight and obese hemodialyzed patients.

BACKGROUND: The body composition in overweight and obese hemodialyzed patients (HD) remains ill-defined. This study evaluates in HD patients the influence of body size, as indicated by body mass index (BMI, kg/m(2)), on body composition by measuring bioimpedance analysis (BIA)-derived variables (phase angle (PA), fat-free mass (FFM) and body cell mass (BCM). METHODS: We studied 50 Caucasian patients (mean age 62.8+/-9.2 y) on standard bicarbonate hemodialysis for at least 12 months who regularly achieved dry weight in post-HD, received similar dialysis doses and were free from inflammation/infection. Thirty-eight gender- and age-matched healthy subjects were included as controls (CON). Both HD and CON were divided into three groups on the basis of their BMI(kg/m2) 18.5-24.9, normal-weight (NW); 25-29.9, overweight (OW); and > or =30, obese (OB). In HD patients, BIA was performed 30 min after the end of dialysis. RESULTS: Seven patients were obese (12%) while 16 were overweight (32%); in CON, 12 were obese (31%) and 12 overweight (31%). BIA-measured extracellular water was comparable in all groups. PA, which was similar in normal-weight HD and CON (6.2+/-0.9 degrees and 6.3+/-0.8 degrees ), decreased in OW- and OB-HD patients (5.3+/-1.0 degrees and 5.2+/-0.6 degrees, respectively; P<0.05 vs NW-HD) while it was unchanged in OW- and OB-CON (6.1+/-0.8 degrees and 5.9+/-0.5 degrees, P<0.05 vs respective HD groups). In OW and OB patients, the lower PA values were coupled with a major reduction of BIA-derived percentage BCM and FFM (P<0.05 vs NW-HD, and vs OW- and OB-CON). In patients, PA and BCM correlated with anthropometry-measured FFM. Of note, serum albumin and protein catabolic rate were significantly reduced in OB patients. CONCLUSION: In overweight and obese HD patients, BIA-derived FFM, BCM and PA are significantly lower with respect to normal-weight patients and BMI-matched controls. These abnormalities of body composition are coupled with reduction of anthropometric measures of lean mass and a decrease of protein intake that, however, becomes significant only in the obese. We therefore suggest that overweight and obese HD patients are at risk of protein malnutrition in spite of excessive energy intake. BIA may be considered as a useful diagnostic tool to detect such a condition early.

Comparison of vector and conventional bioelectrical impedance analysis in the optimal dry weight prescription in hemodialysis.

BACKGROUND: Dry weight prescription is commonly based on symptoms induced by inappropriate fluid removal by hemodialysis (HD). Aim of this study was to compare the assessment of volume status by conventional bioelectrical impedance analysis (BIA) and the resistance-reactance (RXc) graph method in HD patients achieving their target dry weight determined on clinical criteria. METHODS: We studied 39 HD patients (23 males and 16 females, mean age 52 +/- 17 years, dialytic age 41.2 +/- 37 months). Dry weight, prescribed according to the standard clinical criteria, was constantly achieved in the last 3 months. Patients symptom-free over the last 3 months were defined as asymptomatic. Patients with either muscular cramps or hypotensive episodes were defined as symptomatic. Thirty-three healthy volunteers (11 males, 22 females, mean age 50 +/- 11 years) constituted the control group. Standard, single frequency (50 kHz), tetrapolar, BIA measurements were obtained in controls, and in patients before, every 60 min, and 30 min after one HD session. Total body water (TBW), and extracellular water (ECW) were calculated using conventional BIA regression equations. In both groups, tissue hydration was also assessed by the RXc graph method. RESULTS: On the basis of 95% tolerance interval (mean +/- 2 SD) for the ECW (%) calculated in healthy subjects (ECW = 35-44%), HD patients were divided into 3 groups according to their post-HD ECW: 72% normohydrated with ECW 35-44%, 10% overhydrated with ECW >44%, and 18% underhydrated with ECW <35%. Patients were also classified into 3 categories according to the RXc graph method: 38% normohydrated with vectors within the reference 75% tolerance ellipse, 0% overhydrated with short vectors below the lower pole of the 75% tolerance ellipse, and 62% underhydrated with long vectors above the upper pole of the 75% tolerance ellipse. The progressive removal of body fluid during HD treatment was associated with a progressive increase in both impedance vector components, R and Xc. Eleven of thirty-nine patients (28%) were symptomatic during HD treatment in the last 3 months. The majority of these (73%) were classified as normohydrated according to ECW estimates, while 9 and 18% were classified as over- and underhydrated, respectively. This frequency distribution was significantly different from that obtained with the RXc graph method (chi(2) = 6.9, p = 0.03) where the majority (73%) were classified as underhydrated, while 0 and 27% were classified as over- and normohydrated, respectively. The frequency distribution of the 28 asymptomatic patients also significantly differed between conventional BIA and RXc graph hydration categories (chi(2) = 10.8, p = 0.005), since 11, 71 and 18% vs. 0, 43 and 57% of patients were classified as over-, normo-, and underhydrated, respectively. CONCLUSIONS: The classification of volume status based on conventional BIA was insensitive to either clinical situation (presence or absence of symptoms). In contrast, the classification based on the RXc graph was consistent with the clinical course in symptomatic patients (73% dehydrated, and 27% normohydrated), while it did not reflect the clinical course in asymptomatic patients, 57% of whom were classified as (already) underhydrated. A longitudinal study will establish the clinical usefulness of RXc graph indications in asymptomatic patients.

Histamine plasma levels and elimination diet in chronic idiopathic urticaria.

OBJECTIVE: The aim of this study was to evaluate the effects of an oligoantigenic and histamine-free diet on patients affected with chronic idiopathic urticaria (CIU). DESIGN: Ten patients with chronic idiopathic urticaria were prescribed an oligoantigenic and histamine-free diet for 21 days, followed by serial and controlled reintroduction of foods during a further 70 days. Modification in clinical illness as well as histamine plasma levels, post-heparin plasma diamine oxidase (DAO) and intestinal permeability were evaluated. RESULTS: The oligoantigenic and histamine-free diet induced a significant improvement of symptoms (P<0.05). Moreover, CIU patients on free diet showed higher histamine plasma levels (P<0. 05 vs post-diet and vs controls) that fell to control levels during the oligoantigenic and histamine-free diet. Post-heparin plasma diamine oxidase values were slightly reduced and were unchanged during the diet as well as intestinal permeability, which was always normal in all patients. CONCLUSIONS: These data suggest that histamine plays a major role in chronic idiopathic urticaria. The finding of normal intestinal permeability suggests that a morphological damage of intestinal mucosa should be excluded in these patients. However, the presence of low levels of post-heparin plasma diamine oxidase may indicate a subclinical impairment of small bowel enterocyte function that could induce a higher sensitivity to histamine-rich or histamine-producing food. European Journal of Clinical Nutrition (2000) 54, 155-158

A liquid chromatographic assay using a high-speed column for the determination of lamotrigine, a new antiepileptic drug, in human plasma.

A sensitive, specific and rapid liquid-chromatographic method for the determination of the new antiepileptic drug lamotrigine (LTG) in human plasma is described. The method involves the use of a commercially available 3-microns particle size normal-phase column and a microflow-cell-equipped ultraviolet detector. Extraction is carried out with ethyl acetate after alkalinization on a 100-microliters plasma sample containing LTG and 3,5-diamino-6-(2-methoxyphenyl)-1,2,4-triazine as internal standard. The residue is reconstituted with 50 microliters of ethanol, and 5 microliters of the final solution is injected into the column. Elution is carried out at 35 degrees C using n-hexane/absolute ethanol/35% ammonia (80/20/0.25 by volume) as mobile phase at a flow rate of 2.0 ml/min. Detection is at 313 nm. The chromatographic separation requires < 3 min and the sensitivity limit is < 0.1 mg/L. Recovery is 88-96.2%, whereas within-day and day-to-day coefficients of variation are between 4.1 and 7.7%.

Elevation of plasma phenytoin by viloxazine in epileptic patients: a clinically significant drug interaction.

The effect of viloxazine (150-300 mg daily for 21 days) on plasma phenytoin levels at steady state was examined in 10 epileptic patients stabilised on a fixed phenytoin dosage. After starting viloxazine treatment, plasma phenytoin concentrations increased by 37% on average (range 7-94%) from a mean value of 18.8 micrograms/ml at baseline to a mean value of 25.7 micrograms/ml during the last week of combined therapy. In four patients the rise in plasma phenytoin was associated with the development of signs of phenytoin toxicity. Discontinuation of viloxazine resulted in return of plasma phenytoin towards baseline values and disappearance of the clinical symptoms. The mechanism of interaction probably involves inhibition of phenytoin metabolism by viloxazine. Careful monitoring of plasma phenytoin levels is recommended in patients treated with phenytoin who need to be started on viloxazine therapy.

Effect of phenobarbital on the pharmacokinetics of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine.

The single oral dose kinetics of carbamazepine-10,11-epoxide (CBZ-E), the active metabolite of carbamazepine, were studied in six epileptic patients, stabilized on phenobarbital (PB) monotherapy, and in six drug-free health volunteers. The epoxide metabolite was administered as an enteric-coated tablet at the dose of 200 mg to the patients and at the dose of 100 mg to the volunteers. Patients had a significantly higher plasma clearance of CBZ-E than the control group (mean values +/- SD = 220.2 +/- 63.5 versus 112.5 +/- 46.0 ml/h/kg, p less than 0.007) and a significantly shorter plasma half-life (mean values +/- SD = 4.3 +/- 1.0 versus 6.7 +/- 0.8 h, p less than 0.0015). These results suggest that PB induces CBZ-E metabolism.

Evaluation of tricyclic antidepressant plasma levels by an automated enzyme immunoassay (EMIT) in comparison to a high-performance liquid chromatographic method.

A new homogeneous enzyme immunoassay technique (EMIT) for the measurement of plasma levels of amitriptyline, nortriptyline, imipramine, and desipramine was used with an automated procedure and the results were compared to those of a high-performance liquid chromatographic (HPLC) method. Precision of the EMIT test was similar to that of the HPLC method with within-day coefficients of variation in the range of 3.9-10.9% (EMIT) and 3.9-9.6% (HPLC). The day-to-day coefficients of variation ranged from 4.4 to 11.7% for EMIT and from 6.1 to 8.4% for HPLC. Samples from 124 patients were analyzed by both methods and a good correlation was observed for all the four drugs. A paired t test indicated no significant difference for the EMIT and HPLC values. No significant interferences were observed between the tricyclics tested and other commonly associated drugs, such as benzodiazepines and neuroleptics. The new EMIT assay proved to be rapid and easy to perform and showed sufficient reliability and reproducibility to be used for either emergency or routine analysis.

Carbamazepine-viloxazine interaction in patients with epilepsy.

In six depressed epileptic patients stabilised on carbamazepine therapy, addition of the antidepressant agent viloxazine (300 mg/day for three weeks) induced a marked (average 55%) increase in steady-state plasma carbamazepine concentration. The concentration of the active metabolite carbamazepine-10,11-epoxide also increased during viloxazine therapy, but to a lesser extent (16%). In three patients, these effects were associated with symptoms of carbamazepine intoxication, which regressed rapidly when plasma carbamazepine and carbamazepine-10,11-epoxide levels returned to baseline values after discontinuation of viloxazine. In a seventh patient, viloxazine had to be discontinued after only two weeks because of severe side effects associated with a striking elevation of carbamazepine and carbamazepine 10,11-epoxide levels (by 197% and 137% respectively). Although viloxazine appears to be one of the few antidepressants which can be used safely in patients with epilepsy these results indicate that the drug should be prescribed with great caution in subjects treated with carbamazepine. The mechanism of the interaction probably involves inhibition of the metabolism of both carbamazepine and its active epoxide metabolite.

Pharmacokinetics of the antidepressant drug viloxazine in normal subjects and in epileptic patients receiving chronic anticonvulsant treatment.

In order to evaluate the influence of chronic antiepileptic drug treatment on the kinetics of the antidepressant viloxazine (VLX), six drug-free control subjects and six epileptic patients treated with one or two anticonvulsants (phenobarbital, carbamazepine or phenytoin) were given a single oral dose of VLX (200 mg). On a separate occasion, the patients were also given 200 mg VLX by IV infusion. Plasma VLX levels were determined by GLC. Following oral dosing, VLX was rapidly absorbed from the gastrointestinal tract (peak levels at 0.5-4 h); plasma level profiles showed a considerable interindividual variability but did not differ significantly between patients and controls. Terminal half-lives were 4.3 +/- 1.5 h in the patients and 4.3 +/- 1.8 h in the controls. Clearance and volume of distribution calculated after IV dosing in the patients were 124 +/- 11 ml h-1 kg-1 and 0.73 +/- 0.28 l/kg, respectively. The absolute oral availability was 85 +/- 14%. At variance with findings reported for other antidepressants, VLX kinetics do not appear to be significantly altered by concurrent treatment with enzyme-inducing antiepileptic drugs.