Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults.

BACKGROUND: Postoperative adynamic bowel atony interferes with recovery following abdominal surgery. Prokinetic pharmacologic drugs are widely used to accelerate postoperative recovery. OBJECTIVES: To evaluate the benefits and harms of systemic acting prokinetic drugs to treat postoperative adynamic ileus in patients undergoing abdominal surgery. SEARCH STRATEGY: Trials were identified by computerised searches of the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the Cochrane Colorectal Cancer Group specialised register. The reference lists of included trials and review articles were tracked and authors contacted. SELECTION CRITERIA: Randomised controlled parallel-group trials (RCT) comparing the effect of systemically acting prokinetic drugs against placebo or no intervention. DATA COLLECTION AND ANALYSIS: Four reviewers independently extracted the data and assessed trial quality. Trial authors were contacted for additional information if needed. MAIN RESULTS: Thirty-nine RCTs met the inclusion criteria contributing a total of 4615 participants. Most trials enrolled a small number of patients and showed moderate to poor (reporting of) methodological quality, in particular regarding allocation concealment and intention-to-treat analysis. Fifteen systemic acting prokinetic drugs were investigated and ten comparisons could be summarized. Six RCTs support the effect of Alvimopan, a novel peripheral mu receptor antagonist. However, the trials do not meet reporting guidelines and the drug is still in an investigational stage. Erythromycin showed homogenous and consistent absence of effect across all included trials and outcomes. The evidence is insufficient to recommend the use of cholecystokinin-like drugs, cisapride, dopamine-antagonists, propranolol or vasopressin. Effects are either inconsistent across outcomes, or trials are too small and often of poor methodological quality. Cisapride has been withdrawn from the market due to adverse cardiac events in many countries. Intravenous lidocaine and neostigmine might show a potential effect, but more evidence on clinically relevant outcomes is needed. Heterogeneity among included trials was seen in 10 comparisons. No major adverse drug effects were evident. AUTHORS' CONCLUSIONS: Alvimopan may prove to be beneficial but proper judgement needs adherence to reporting standards. Further trials are needed on intravenous lidocaine and neostigmine. The remaining drugs can not be recommended due to lack of evidence or absence of effect.

Intestinal expression of cytochrome P450 enzymes and ABC transporters and carbamazepine and phenytoin disposition.

OBJECTIVES: Interindividual variability in intestinal absorption and bioavailability might contribute to inadequate control of seizures under treatment with carbamazepine and phenytoin. We therefore correlated intestinal expression levels and genetics of CYP3A4, CYP2C9/19, MDR1 and MRP2 with dose requirement and plasma levels of carbamazepine and phenytoin. MATERIALS AND METHODS: Epileptic patients on carbamazepine (n = 29) or phenytoin (n = 15) were stratified into a 'high'-dose (carbamazepine > or =800 mg/day, phenytoin > or =300 mg/day) and a 'low'-dose group (carbamazepine < or =600 mg/day, phenytoin < or =200 mg/day). Duodenal biopsies and DNA were obtained for Western blotting and genotyping studies. RESULTS: Low carbamazepine plasma levels showed a trend towards higher intestinal MDR1 expression (P = 0.06). Furthermore, carbamazepine dose was positively correlated with MRP2 expression (P = 0.1). Moreover, MDR1 expression and carbamazepine and phenytoin dose requirement was influenced by the genotype in position 2677 and 3435 of the MDR1 gene. CONCLUSION: Differences in intestinal MDR1 and MRP2 expression may influence carbamazepine and phenytoin disposition and may account for interindividual pharmacokinetic variability.

Alveolar echinococcosis of the liver in an adult with human immunodeficiency virus type-1 infection.

We describe a patient with human immunodeficiency virus type-1 (HIV) infection and alveolar echinococcosis (AE) with a focus on two messages. Despite being severely immunocompromised over years the patient exhibited a long-term asymptomatic course of AE. This is in clear contrast to reports describing accelerated courses of AE in immunocompromised patients. The patient had therapeutic mebendazole drug levels with only 1/10 of the normal drug dose. He was co-treated with protease inhibitors for his HIV infection. These drugs are known as strong inhibitors of cytochrome P450 3A4 (CYP3A4)-dependent metabolism. We speculate that benzimidazoles and protease inhibitors interfere at the CYP3A4-level. The first report of co-infection of HIV and accelerated AE was in a young girl with an extremely low CD4 cell count and an abrogated lymphoproliferative responsiveness to parasite antigen stimulation. Since the CD4 cell count in our patient remained in the range of 27-150 cells/microl, we speculate that there was a critical threshold of immunosupression for constraining AE. Initial treatment with albendazole for AE added to the current highly active antiretroviral treatment (HAART), and suppressive toxoplasmosis therapy became complicated by pancytopenia. After full recovery of the bone marrow, mebendazole was introduced with a new HAART and the previously prescribed toxoplasmosis maintenance therapy. Surprisingly, efficient mebendazole levels were achieved with an uncommonly low dose. These observations suggest that the benzimidazoles, albendazole and mebendazole, may interact with protease inhibitors, which are known for their strong inhibition of the CYP3A4.

Progressive changes in patients' lives after psychotherapy: which treatment effects support them?

The endurance of psychotherapeutic effects after conclusion of inpatient treatment is examined in a follow-up study of 49 patients with psychosomatic, neurotic, and personality disorders. The perspective is not symptomatological but rather relates to the concrete changes occurring in the lives of the patients after treatment. The investigators hypothesized that the probability of progressively coping with life demands depends on the extent to which patients have gained insight into their central psychological problems. Using the Heidelberg Structural Change Scale (HSCS) to gauge the extent to which patients succeed in gaining cognitively and emotionally definitive insight into their intrapsychic conflicts and the structural vulnerabilities determining their condition, the authors were able to confirm their hypothesis. The HSCS, compared with other measures, offered the only possibility of predicting progressive (i.e., symptomatic) changes. The authors concluded that the demands of external life present opportunities for therapy success to be realized as progressive changes and that these changes can form a basis for further positive development.

P-glycoprotein-mediated transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin.

Digoxin is a drug with a narrow therapeutic index, which is substrate of the ATP-dependent efflux pump P-glycoprotein. Increased or decreased digoxin plasma concentrations occur in humans due to inhibition or induction of this drug transporter in organs with excretory function such as small intestine, liver and kidneys. Whereas particle size, dissolution rate and lipophilic properties have been identified as determinants for absorption of digitalis glycosides, little is known about P-glycoprotein transport characteristics of digitalis glycosides such as digitoxin, alpha-methyldigoxin, beta-acetyldigoxin and ouabain. Using polarized P-glycoprotein-expressing cell lines we therefore studied whether these compounds are substrates of P-glycoprotein. Polarized transport of digitalis glycosides was assessed in P-glycoprotein-expressing Caco-2 and L-MDR1 cells (LLC-PK1 cells stably transfected with the human MDR1 P-glycoprotein). Inhibition of P-glycoprotein-mediated transport of these compounds in Caco-2 cells was determined using the cyclosporine analogue PSC-833 (valspodar) as inhibitor of P-glycoprotein. No polarized transport was observed for ouabain. However, basal-to-apical transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin was greater than apical-to-basal transport in Caco-2 and L-MDR1 cells. In Caco-2 cells net transport rates of these compounds were similar to those of digoxin (digoxin: 16.0+/-4.4%, digitoxin: 15.0+/-3.3%, beta-acetyldigoxin: 16.2+/-1.6%, alpha-methyldigoxin: 13.5+/-4.8%). Furthermore, polarized transport of these compounds could be completely inhibited by 1 microM PSC-833. In summary, these data provide evidence that not only digoxin, but also digitoxin, alpha-methyldigoxin and beta-acetyldigoxin are substrates of P-glycoprotein.

Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein.

Proton pump inhibitors are a class of drugs which are widely prescribed for acid-related diseases. They are primarily metabolized by CYP2C19 and CYP3A4. It is unknown so far whether proton pump inhibitors are also substrates of the ATP-dependent efflux transporter P-glycoprotein. Moreover, it is not established whether proton pump inhibitors are also inhibitors of P-glycoprotein function. The aim of our study was therefore to characterize omeprazole, lansoprazole and pantoprazole as P-glycoprotein substrates and inhibitors. Polarized transport of these compounds was assessed in P-glycoprotein-expressing Caco-2 and L-MDR1 cells. Inhibition of P-glycoprotein-mediated transport was determined using the cyclosporine analogue PSC-833 (valspodar) as P-glycoprotein inhibitor. Inhibition of efflux transport by omeprazole, lansoprazole and pantoprazole was assessed using digoxin as P-glycoprotein substrate. At concentrations of 5 microM, basal-to-apical transport of omeprazole, lansoprazole and pantoprazole was greater than apical-to-basal transport in Caco-2 and L-MDRI cells. Addition of PSC-833 (1 microM) showed a clear effect only for lansoprazole, suggesting that other transporters contribute to omeprazole and pantoprazole cellular translocation. Furthermore, all of the tested compounds inhibited digoxin transport with IC50 values of 17.7, 17.9 and 62.8 microM for omeprazole, pantoprazole and lansoprazole, respectively. In summary, our data provide evidence that proton pump inhibitors are substrates and inhibitors of P-glycoprotein. These findings might explain some of the drug interactions with proton pump inhibitors observed in vivo.

Containers for waste causing peritonitis in CAPD patients.

Fungal infection is a rare cause of peritonitis in patients on chronic peritoneal dialysis. In this population, fungi are found in less than 2 percent of all cases of primary episodes of peritonitis (1). More often, a primary bacterial peritonitis treated with antibiotic therapy leads to secondary fungal infection (2). Candida species cause 74.5% of the episodes of fungal peritonitis (2). The fungi invade the peritoneal cavity from the skin peri- or intraluminally through the catheter (3). Filamentous fungi are rare (4,5). Treatment of fungal peritonitis commonly consists of removal of catheter and antifungal drugs (3). Here we describe two cases of fungal peritonitis caused by mycelial fungi, where the source of the microorganism could be special containers used for biological waste, which are popular in Germany

[Typical counseling processes in prenatal diagnosis--an explorative study]. / Typische Beratungsinhalte in der Pränataldiagnostik--eine explorative Studie.

A qualitative study is presented, investigating the subjective experiences of counsellors in consulting pregnant women expecting a child with genetic defects. The aim of the study was an exploration of consultation criteria that were used in these consultations, to systematically expand the currently used theoretical based consultation concepts by the perspectives of those involved in the consultation process. The study is part of a collaborative study, dealing with the development of consultation criteria for pregnant women. Data consist of extensive written consultation transcripts, describing typical case setting at different time points during a consultation process. We used a content-analytical approach to systematically categorize the variety of single topics mentioned in these transcripts. Typical consultation settings at different time points during consultation were compared. Data are presented using illustrated text material.

Stimulated IFNgamma and IL-10 secretion of blood mononuclear cells in patients on renal replacement therapies show different secretion patterns.

Infection is still a leading cause of morbidity and mortality in patients on renal replacement therapy (RRT). Although the role of the immune system is of great importance, little is known about the influence of the mode of RRT to the preferential excretions of regulator cytokines of mononuclear cells. Therefore, we investigated the stimulated IFNgamma (Th1) and IL-10 (Th2) secretions of mononuclear cells from patients on RRT. Blood was drawn from 10 controls, 15 patients on hemodialysis (HD), 15 on peritoneal dialysis (PD), and 10 after kidney transplantation (Tx). The cells were separated, and phytohemagglutinine (PHA) was added for stimulation. After 0, 6, and 24 h, IFNgamma and IL-10 (pg/ml) were measured by enzyme-linked immunosorbent assay. IFNgamma secretion was significantly enhanced 6 (p < 0.001) and 24 h (p = 0.002) after stimulation in all groups (in mean +/- SEM). The analysis of the subgroups 6 h after adding PHA showed significant differences (p = 0.0239) with the lowest IFNgamma in Tx (16 +/- 5) and the highest in PD (79 +/- 30). For IL-10, secretion was enhanced in all groups 6 h after stimulation (p < 0.0116). The lowest secretions were seen in HD (18 +/- 8) and controls (27 +/- 9); the highest secretions were in Tx (98 +/- 20) and PD (57 +/- 12). The differences between HD and Tx (p < 0.01) and HD versus PD (p = 0.05) were significant. The stimulated cytokine secretion of blood mononuclear cells is preserved with RRT. The modes of RRT could influence the pattern of cytokine secretion. Surprisingly, the cells from patients on PD showed enhanced IL-10 secretion compared to HD. Presumably, this is due to the chronic contact of peritoneal dialysis fluids with monocytes and the lymphatic system in PD.

A new lactate-based, plasticizer-free, neutral peritoneal dialysis fluid provided in a two-compartment system: effect on peripheral leukocyte function.

BACKGROUND: A new neutral peritoneal dialysis fluid (PDF; Balance) provided in a two-compartment bag (pH 7.4, no plasticizers, minimal glucose degradation products - GDP) was investigated in comparison with a neutral control (Hanks' balanced salt solution with gelatin 0.1%) and other PDFs with standard properties and plasticizers (Andy plus, pH 5.2, GDP), plasticizer free (stay safe, pH 5.2, GDP), and in addition plasticizer free after sterile filtration instead of heat sterilization (pH 5.2) regarding the function of peripheral blood leukocytes. METHODS: Blood was drawn from 12 volunteers, and blood monocytes (MN) and polymorphonuclear leukocytes (PMNL) were collected. The cells were incubated for 30 min in control medium and the PDFs: glucose 1.5% (83 mmol/l) and 4.25% (238 mmol/l). Respiratory burst of cells was evaluated by chemiluminescence and superoxide (SO) generation after stimulation with phorbol myristate acetate. RESULTS: In comparison with the control medium, incubation of MN in the two-compartment PDF showed preservation of respiratory burst. In contrast, the incubation of MN in standard PDF and plasticizer-free PDF showed impaired functions. The same was found for PMNL. SO anion measurement in MN and PMNL after incubation in the new two-compartment PDF also showed preservation of cell function in comparison with the control medium. The incubation of PMNL in standard PDF and plasticizer-free PDF with a high glucose content showed depressed SO anion generation. CONCLUSIONS: These in vitro data demonstrate a better preservation of in vitro phagocyte function with adaptation of pH and reduction of glucose, GDP, and plasticizers in PDFs. The best results are achieved with the two-compartment, lactate-based neutral PDF.

Characterization of the major metabolites of verapamil as substrates and inhibitors of P-glycoprotein.

Verapamil is subject to extensive oxidative metabolism mediated by cytochrome P450 enzymes with less than 5% of an oral dose being excreted unchanged in urine. Furthermore, verapamil is known to be a potent inhibitor of P-glycoprotein function. There is evidence from in vivo investigations that some verapamil metabolites might be actively transported. The aim of the present study was to investigate P-glycoprotein-mediated transport and inhibition properties of verapamil and its metabolites norverapamil, D-620, D-617, and D-703. Polarized transport of these compounds was assessed in P-glycoprotein-expressing Caco-2 and L-MDR1 cells (LLC-PK1 cells stably transfected with human MDR1-P-glycoprotein). Inhibition of P-glycoprotein-mediated transport by these compounds was determined using digoxin as P-glycoprotein substrate. At concentrations of 5 microM, significant differences between basal-to-apical and apical-to-basal apparent permeability coefficients were observed for D-617 and D-620 in all P-glycoprotein-expressing cell monolayers, indicating that both are P-glycoprotein substrates. In contrast, no P-glycoprotein-dependent transport was found for verapamil, norverapamil, and D-703 in Caco-2 cells and for D-703 in L-MDR1 cells. Moreover, verapamil, norverapamil, and D-703 inhibited P-glycoprotein-mediated digoxin transport with IC(50) values of 1.1, 0.3, and 1.6 microM, respectively, whereas D-617 and D-620 did not (at concentrations up to 100 microM). We conclude that verapamil phase I metabolites exhibit different P-glycoprotein substrate and inhibition characteristics, with the N-dealkylated metabolites D-617 and D-620 being P-glycoprotein substrates and norverapamil and D-703 being inhibitors of P-glycoprotein function, which may influence P-glycoprotein-dependent drug disposition and elimination.

Influence of plasticizer-free CAPD bags and tubings on serum, urine, and dialysate levels of phthalic acid esters in CAPD patients.

OBJECTIVES: To evaluate the impact of a plasticizer-free device on exposure to di-(2-ethylhexyl) phthalate (DEHP) and its major metabolites in patients on continuous ambulatory peritoneal dialysis (CAPD). DEHP is the most commonly used plasticizer in polyvinyl chloride (PVC) products; it is added to CAPD bags in order to improve the flexibility of the material. Since DEHP leaches out of the plastic matrix, patients on CAPD are exposed to considerable amounts of DEHP and its metabolites. DESIGN: A prospective cross-over study. SETTING: Department of nephrology in a teaching hospital. PARTICIPANTS: Six patients (4 female, 2 male) stable on peritoneal dialysis (PD) for at least 6 months. INTERVENTIONS: Patients were switched from a plasticizer-containing PVC CAPD system (A.N.D.Y. Plus, Fresenius Medical Care, Bad Homburg, Germany) to a polyolefine-made plasticizer-free system (stay-safe, Fresenius). MAIN OUTCOME MEASURES: Prior to and 42 days after the switch, 24-hour effluent dialysate and urine collections were performed and 10 mL blood was drawn. Concentrations of DEHP, mono-(2-ethylhexyl) phthalate (MEHP), phthalic acid (PA), and 2-ethylhexanol (2-EH) in urine, dialysate, and serum were determined using gas chromatography/mass spectrometry. RESULTS: Complete data were obtained from 5 patients. Serum levels of PA decreased significantly during the study period (0.137 +/- 0.078 mg/L vs 0.124 +/- 0.049 mg/L, p = 0.04), and the respective levels of DEHP decreased insignificantly (0.097 +/- 0.076 mg/L vs 0.069 +/- 0.046 mg/L, p = 0.07), whereas the concentrations of MEHP and 2-EH remained unchanged. Urine concentrations of PA were high (0.81 +/- 0.69 mg/L) but did not change substantially (0.70 +/- 0.50 mg/L). Effluent dialysate concentrations of MEHP and PA decreased significantly (0.0176 +/- 0.004 mg/L vs 0.0040 +/- 0.0007 mg/L, p = 0.043 and 0.158 +/- 0.056 mg/L vs 0.111 +/- 0.051 mg/L, p = 0.043, respectively). CONCLUSIONS: Although PD patients seem to be exposed to other sources of phthalates in addition to dialysis, use of plasticizer-free devices may help to reduce potentially immunosuppressive exposure to phthalate esters.

Effects of L-carnitine on leukocyte function and viability in hemodialysis patients: A double-blind randomized trial.

Excess morbidity and mortality among long-term hemodialysis patients because of infectious complications is partly caused by an impairment of cellular immune defense. We hypothesized this impairment is related to an abnormal carnitine metabolism also present in these patients. In a double-blind, randomized, placebo-controlled trial, we investigated the effect of L-carnitine on phagocytic function and viability of blood leukocytes in 17 patients undergoing maintenance hemodialysis. After an observation period of 1 month, the patients received either 10 mg/kg of L-carnitine or placebo intravenously at the end of each hemodialysis session over a period of 4 months. Leukocyte oxidative metabolism was measured by means of luminol-enhanced chemiluminescence and superoxide generation after stimulation with Staphylococcus aureus or phorbol myristate acetate. Killing capacity and phagocytosis of radiolabeled staphylococci were determined. A lactate dehydrogenase (LDH) release test was applied to assess cell viability. We were unable to show an effect of L-carnitine on phagocytic function and viability in vivo. Several clinical parameters were observed during the trial. No statistically significant differences concerning dialysis-related morbidity, anemia, or reduction of blood urea nitrogen and creatinine levels were detected. Additionally, we tested the effect of L-carnitine on phagocytic function after in vitro incubation of blood leukocytes, which also showed no changes. LDH release was decreased, indicating an improved viability of these cells. The latter results were found after in vitro incubation of cells, but could not be confirmed in vivo. In summary, we could not show beneficial effects of L-carnitine administration in hemodialysis patients for the dosage and duration of treatment stated, either on phagocytic function and viability or on the clinical and biochemical parameters observed.

[Severe nephrotic syndrome with reversible acute kidney failure in lupus-associated membranous nephropathy]. / Schweres nephrotisches Syndrom mit reversiblem akuten Nierenversagen bei lupusassoziierter membranöser Nephropathie.

HISTORY AND CLINICAL FINDINGS: A 20 year old, previously healthy woman presented with a four week history of progressive oedema of the legs and the eyelids and a weight gain of 10 kg. INVESTIGATIONS: Biochemical tests revealed a nephrotic syndrome with a protein-loss in urine of 13.6 g/24 hours and a serum-albumin of 1.2 g/dl. Serological tests showed positive response for antinuclear antibodies, anti-double-stranded-DNA antibodies and cardiolipin antibodies. Renal histology revealed a lupus-associated diffuse membranous nephropathy (WHO-type Vd). DIAGNOSIS, TREATMENT AND COURSE: We first started a treatment regimen with oral steroids and intravenous loop-diuretics without improvement of the nephrotic syndrome. Two weeks after initial presentation the patient developed dialysis-dependent, acute renal failure. Having excluded a renal vein-thrombosis and the transition to diffuse proliferative form of the glomerulonephritis we suggested a nephrotic etiology of the acute renal failure. We initiated cyclophosphamide pulse-therapy which led to dramatic improvement of the nephrotic syndrome after the first cycle with reduction of protein-loss to 6 g/24 hours. Concurrently renal function recovered and treatment with hemodialysis could be stopped after 3 weeks. CONCLUSION: Acute renal failure in nephrotic syndrome has also to be considered in an acute form of a membranous lupus nephritis. Renal recovery is much better when acute renal failure is caused by nephrotic syndrome.

Pharmacokinetics of morphine and its glucuronides following intravenous administration of morphine in patients undergoing continuous ambulatory peritoneal dialysis.

BACKGROUND: Conjugation with glucuronic acid represents the major route of biotransformation of morphine. The glucuronides morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are eliminated via the kidneys. Therefore, chronic renal failure should affect the disposition of M3G and M6G. Numerous patients undergoing long-term continuous ambulatory peritoneal dialysis (CAPD) require pain treatment with morphine. There are only limited data available about the disposition of morphine and its active metabolites M6G and M3G in patients on CAPD. We therefore investigated the pharmacokinetics of morphine and its metabolites in CAPD patients. METHODS: This was a single intravenous dose pharmacokinetic study in 10 CAPD patients (1 female, 9 male, age 31-69 years). Morphine-hydrochloride (Mo) (10 mg) was administered intravenously. Serum, urine, and dialysate samples were collected during 24 h. GC-MS-MS and HPLC-MS methods were used to quantify respectively morphine and morphine glucuronides. RESULTS: While systemic clearance of morphine (1246+/-240 ml/min) was in the range observed in patients with normal kidney function, both M3G and M6G showed substantial accumulation. The area under the concentration-time curve (AUC) ratio of M3G:Mo (33.4+/-7.1) and of M6G:Mo (12.2+/-3.2) was 5.5 and 13.5 times higher than in patients with normal kidney function. Renal clearances of morphine, M3G, and M6G (morphine 3.0+/-2.5 ml/min; M3G 3.9+/-2.2 ml/min; M6G 3.6+/-2.2 ml/min) and dialysate clearances (morphine 4.1+/-1.3 ml/min; M3G 3.2+/-0.7 ml/min; M6G 3.0+/-0.8 ml/min) were extremely low. Therefore the accumulation of M6G and M3G is readily explained by kidney failure which is not compensated by CAPD. CONCLUSION: Accumulation of M3G and M6G is due to the substantially lowered clearance by residual renal function and peritoneal dialysis. In view of the accumulation of potential active metabolites, subsequent investigations have to assess the frequency of side-effects in patients on CAPD.

Phthalic acid is the main metabolite of the plasticizer di(2-ethylhexyl) phthalate in peritoneal dialysis patients.

Di(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer in polyvinyl chloride (PVC) plastics, and is therefore a major constituent of continuous ambulatory peritoneal dialysis (CAPD) bags. Because DEHP is not chemically bound, it leaches out of the plastic matrix. Recently, we found that leukocyte function in vitro is impaired by a mixture of metabolites of DEHP. In the present study, we investigated the metabolism of DEHP in patients on CAPD. The study group consisted of 10 stable patients, on CAPD for at least 6 months, using a plasticizer-containing PVC PD system [ANDY Plus (Fresenius Medical Care, Bad Homburg, Germany)]. Effluent dialysate and urine samples were collected over 24 hours, and a 10 mL blood sample was drawn. Concentrations of DEHP and its metabolites mono(2-ethylhexyl) phthalate (MEHP), phthalic acid (PA), and 2-ethylhexanol (2-EH) were determined in urine, dialysate, and serum using gas chromatography/mass spectrometry. Additionally, the degree of glucuronidation of the phthalic acid esters in urine were determined. In serum, dialysate, and urine, PA was the predominant metabolite of DEHP (0.205 +/- 0.067 mg/L, 0.284 +/- 0.180 mg/L, and 1.34 +/- 1.00 mg/L, respectively), but concentrations of MEHP were low (0.0100 +/- 0.0056 mg/L, 0.022 +/- 0.008 mg/L, 0.011 +/- 0.0064 mg/L, respectively). Urinary MEHP was glucuronidated to approximately 15%. PA was 35% eliminated as a glucuronide. Unlike healthy subjects, PD patients do not eliminate DEHP mainly in the form of MEHP or MEHP metabolites. They further break these compounds down to PA. The fact that concentrations of PA in urine exceed by far the respective serum concentrations indicates that PA is secreted by the kidney. Further research on the toxicological aspects of plasticizers in uremic patients should take these findings into account.