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W Arns

Publications and source records attributed to W Arns.

At least 19 recordsLinked to original sources
PubMed2006

Conversion to enteric-coated mycophenolate sodium from various doses of mycophenolate mofetil: results of a prospective international multicenter trial in maintenance renal transplant patients receiving cyclosporine.

Conversion from mycophenolate mofetil (MMF, CellCept) to enteric-coated mycophenolate sodium (EC-MPS, myfortic) is safe and effective in renal transplant patients treated with the standard dose of 2 g MMF. In this 6-month, international, multicenter, open-label, single-arm trial, a large cohort of maintenance renal transplant patients receiving different doses of MMF were converted under normal clinical conditions to equimolar doses of EC-MPS. Mean calculated creatinine clearance remained stable from the time of study entry (59.6 +/- 19.7 mL/min) to the end of the study (58.3 +/- 19.8 mL/min). Adverse events were reported by 152 patients (67%), with gastrointestinal complications being observed in 45 patients (20%). Thirty-three patients (15%) experienced adverse events or infections with a suspected relation to EC-MPS, including one case of anemia and two cases of leukopenia. Eleven patients (4.9%) required a reduction in EC-MPS dose and seven patients (3.1%) permanently discontinued EC-MPS owing to adverse events. At month 6 after conversion, five patients (2.2%) experienced biopsy-proven acute rejection. There were no graft losses or deaths. These data support earlier findings that stable maintenance renal transplant patients receiving MMF with cyclosporine with or without corticosteroids can be converted to EC-MPS with no compromise in efficacy and tolerability, and no adverse effect on renal function.

Adult↗
PubMed2006

Absorption characteristics of EC-MPS--an enteric-coated formulation of mycophenolic sodium.

UNLABELLED: Enteric-coated mycophenolate sodium is an advanced formulation delivering mycophenolic acid (MPA), designed to improve MPA-related upper gastrointestinal adverse events by delaying MPA release until the small intestine. OBJECTIVE: Two studies were undertaken to identify the absolute bioavailability and dose-proportionality of enteric-coated mycophenolate sodium in stable renal transplant patients receiving cyclosporine. METHODS: Study 1: The mean MPA AUC(0-t) was shown to be greater after MPA infusion than after oral enteric-coated mycophenolate sodium (42.1 vs. 28.9 microg x h/ml). Mean absolute bioavailability was 0.71 +/- 0.21 (SD). Study 2: The AUC(0-t) and C(max) for MPA were proportional to the dose of enteric-coated mycophenolate sodium, similarly mean AUC(0-infinity) and C(max) for MPA glucuronide were proportional to dose administered. RESULTS AND CONCLUSIONS: In patients receiving cyclosporine the absolute bioavailability of MPA provided by enteric-coated mycophenolate sodium is equivalent to that provided by mycophenolate mofetil when administered in combination with cyclosporine, and exhibits dose-proportionality. Enteric-coated mycophenolate sodium was well tolerated from 180 - 2,160 mg with no serious adverse events reported.

Administration, Oral↗
PubMed2005

Cyclosporine C2 levels in de novo renal allograft recipients: a German multicenter prospective observational study.

This ongoing multicenter prospective observational study was undertaken in de novo renal allograft recipients managed with cyclosporine (CsA) trough (C0) and 2-hour postdose (C2) level monitoring at defined times so as to assess the risk for an acute rejection episode or allograft dysfunction. The renal transplant recipients (n = 159) were enrolled at 11 German centers. The 6-month posttransplant data from 138 patients were evaluable for this interim analysis. Mean C2 levels (ng/mL), which were measured by liquid chromatography-tandem mass spectrometry at a central laboratory, were: days 3 to 5: 873.1 +/- 391.9; days 7 to 10: 939.1 +/- 422.8; days 14 to 28: 1116.3 +/- 497.6; 3 months: 905.0 +/- 316.8; and after 6 months: 787.0 +/- 276.5. To identify patients at higher risk for acute rejection or allograft dysfunction, we calculated the relative CsA absorption capacity (C2 [ng/mL]/morning dose [mg/kg]; CsA-Abs), yielding mean values on days 3 to 5: 284.4 +/- 115.1; days 7 to 10: 306.7 +/- 134.8; days 14 to 28: 382.5 +/- 164.7; month 3: 501.5 +/- 168.8; month 6: 512.7 +/- 176.5. Three groups were distinguished by CsA-Abs at days 7 to 10: low absorbers (CsA-Abs < 200), normal absorbers (CsA-Abs 200 to 350), and high absorbers (CsA-Abs > 350). A between-group comparison of absorption level at 6 months posttransplant revealed the incidences of biopsy-proven acute rejection and Cockcroft-Gault formula-based mean glomerular filtration rates of 23.8% and 54.7 +/- 19.0 mL/min, 22.6% and 59.5 +/- 20.7 mL/min, and 17.6% and 67.7 +/- 23.5, respectively. In conclusion, mean C2 levels >1000 ng/mL are attained within 2 to 4 weeks, with CsA-Abs increasing continuously over the first 6 posttransplant months. High CsA absorbers show a propensity toward good allograft function and lower acute rejection rates at 6 months after renal transplantation.

Area Under Curve↗
PubMed2004

Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in maintenance renal transplant patients: preliminary results from the myfortic prospective multicenter study.

Mycophenolate mofetil (MMF), in combination with cyclosporine and corticosteroids, improves long-term graft survival in renal transplant recipients. However, optimal MMF therapy may be limited by gastrointestinal (GI) intolerance, which may result in the need for MMF dose reduction, interruption, or discontinuation, leading to increased risk of acute rejection. Enteric-coated mycophenolate sodium (EC-MPS) is a new formulation delivering mycophenolic acid developed with the aim of improving upper GI tolerability. A large prospective, open-label, multicenter program (myPROMS: myfortic PROspective Multicenter Study) is underway to determine the efficacy and safety of EC-MPS, in combination with cyclosporine microemulsion (CsA; Neoral) in a large population of de novo and maintenance renal transplant recipients. myPROMS consists of one global protocol with 14 subprotocols. Each subprotocol is designed to address further specific objectives, such as specific patient populations, steroid regimens, and various CsA C2 targets. The preliminary data summarized here are from two subprotocols, which investigated the benefits of converting maintenance renal transplant patients receiving MMF to EC-MPS. The 3-month interim analyses suggest that the conversion from MMF to EC-MPS is well tolerated in maintenance renal transplant recipients.

Cyclosporine↗
PubMed2001

[Renal oxalosis with renal failure after infusion of xylitol].

HISTORY AND FINDINGS: Ten days after a complication-free operation for early gastric cancer a 61-year old man had a seizure and acute renal failure. INVESTIGATIONS: A percutaneous renal biopsy was performed to find the cause of the renal failure, which at times required several sessions of haemodialysis. TREATMENT AND COURSE: The seizure was thought to have been due to cerebrovascular deposits of oxalate crystals (renocerebral oxalosis). Parenteral xylitol had been given postoperatively, as a glucose substitute (total dose 1560g), together with other routine drugs. Primary oxalosis and other causes of secondary oxalosis had been excluded. CONCLUSION: Xylitol should not be used parenterally as a glucose substitute (banned in the USA).

Acute Kidney Injury↗
PubMed1995

Concentration-guided strategies in drug development: experience with a cyclosporine analog in transplantation.

A concentration-guided study was designed to maintain adequate immunosuppression and avoid excessive drug exposure while determining steady-state relative bioavailability of two cyclosporine G (CyG) oral formulations in stable renal transplant patients. In period I (week 1), 26 patients taking cyclosporine A (CyA)-based immunosuppressive regimens entered the study. Doses were titrated to maintain trough concentrations within a predefined range, as measured by fluorescence polarization immunoassay (FPIA). Patients were given an oral solution of CyG in period II (weeks 2-3), and a microemulsion capsule formulation of CyG in period III (weeks 4-5), with dose titration as necessary to achieve trough concentrations in a predefined range, as measured by FPIA. Full pharmacokinetic profiles were obtained on the last day of each study period. Treatment with CyA was reinitiated in period IV (week 6) at the same doses as at study entry. All blood samples were analyzed at the conclusion of the study using CyG- and CyA-specific high-performance liquid chromatography (HPLC). When changing from oral solution to capsule for CyG, an average 19% dose reduction was necessary to compensate for the elevated trough concentrations resulting from the increased bioavailability of the capsule formulation. The concentration-guided strategy was successful in avoiding over-exposure, and resulted in comparable values for area under the concentration-time curve (AUC) for both formulations of CyG. Dose normalization of the pharmacokinetic parameters subsequently allowed calculation of the relative bioavailability. Specifically, a faster rate and greater extent of CyG absorption from the capsule than the oral solution were manifested as a slightly earlier time to peak concentration (tmax), an average 44% increase in the maximum concentration (Cmax), and an average 29% increase in AUC. This experience demonstrated that a concentration-guided trial design allowed a drug development question for a compound with a narrow therapeutic index to be addressed safely and directly in the target patient population.

Administration, Oral↗
PubMed1995

Acute effect of cyclosporin on renal function following the initial changeover to a microemulsion formulation in stable kidney transplant patients.

Potential differences in the acute effect of cyclosporin on renal function when dosed orally as the current market formulation or following a milligram-to-milligram conversion to a new microemulsion formulation were investigated in 14 stable kidney transplant patients. The study consisted of three sequential periods of 2 weeks duration each. Patients entered (period I) and completed (period III) the investigation with the market formulation and received the microemulsion formulation in period II; individualized cyclosporin doses remained unchanged throughout the study. Over one steady-state dosing interval at the end of each study period, whole blood cyclosporin pharmacokinetic profiles were assessed in parallel with endogenous creatinine clearances over sequential 1- to 2-h intervals. The rate and extent of cyclosporin absorption were significantly greater (P < 0.01) from the microemulsion formulation with average increases of 73% in peak concentration and 44% in area under the curve compared to the market formulation. Sequential creatinine clearances exhibited a transient decrease with the nadir occurring on average between 4 and 6 h post dose followed by a rapid return to baseline. Specifically in period I on the market formulation, clearances decreased from a baseline of 71.7 +/- 20.6 to a minimum of 51.1 +/- 17.9 ml/min per 1.73 m2 (similar values in period III) and from 76.8 +/- 24.8 to 53.5 +/- 17.5 ml/min 1.73 m2 in period II on the microemulsion. Neither the baseline nor minimum clearances were significantly different among the study periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Within-day consistency in cyclosporine pharmacokinetics from a microemulsion formulation in renal transplant patients.

A new microemulsion formulation of cyclosporine (Sandimmune Neoral) was compared to the commercially available formulation (Sandimmune) in 11 stable renal transplant patients with regard to the consistency in cyclosporine pharmacokinetics between a daytime fasting, and a nighttime nonfasting administration. Daily cyclosporine doses were individualized and administered in equal, divided doses every 12 h as soft gelatin capsules; doses were kept constant throughout the study. Serial blood samples were obtained over a 24-h period (two consecutive dosing intervals) at steady-state for each formulation, and cyclosporine concentrations were determined in whole blood by a specific radioimmunoassay method. Within-formulation consistency in pharmacokinetic parameters between the daytime and nighttime administrations was assessed in terms of bioequivalence criteria. Following the mg-to-mg conversion from the commercial to the microemulsion formulation, area under the curve (AUC) was increased on average by 30% due to absorption-related pharmacokinetic differences, while trough concentrations remained in the therapeutic range. Within each formulation, AUC was bioequivalent when comparing the daytime fasting to the nighttime nonfasting administration. For the commercial formulation, however, there was considerable variation in absorption rate, dampening of peak-trough fluctuation, and elevation of trough concentration following the nighttime nonfasting dose. By contrast, the microemulsion exhibited a more stable concentration-time profile over the two dosing intervals, with bioequivalence in peak-trough fluctuation and trough concentrations. Hence, the steady-state pharmacokinetics of cyclosporine from the microemulsion formulation exhibit greater within-day consistency compared to the commercial formulation in stable renal allograft recipients.

Adult↗
PubMed1987

Graft survival and long-term renal function after sequential conventional cyclosporin A therapy in cadaver kidney transplantation--a prospective randomized trial.

In a prospective randomized trial 50 renal transplant patients (group A) received a sequential course of 14 days conventional immunosuppression (Lymphocytoglobulin (ALG), azathioprine, steroids) and cyclosporin and steroids thereafter, while 50 patients (group B) received the conventional immunosuppression for 7 days followed by cyclosporin and steroids. In the latter group ALG was tolerated for the whole period while in the first group conversion from conventional to cyclosporin A therapy had to be performed after a mean of 11 days, due to ALG intolerance. Actual patient survival rates 1 year posttransplant were 100% in both groups and graft survival rates 96% in group A and 86% in group B (P less than 0.05). There was a mean dialysis frequency per patient of 0.7 +/- 2.0 in group A and 1.8 +/- 3.4 in group B (P = 0.064). Serum creatinine 1 year posttransplant was 1.8 +/- 0.8 mg/dl in group A and 2.2 +/- 1.4 in group B. A total of 58 patients had a serum creatinine of less than 2 mg/dl at the time of conversion to cyclosporin. These patients had a significantly better graft survival rate (98.3%) and serum creatinine 1 year posttransplant (1.6 +/- 0.5 mg/dl) than the 40 patients with a serum creatinine of more than 2 mg/dl at the time of conversion (85%; 2.4 +/- 1.4 mg/dl), indicating that a delayed onset of cyclosporin therapy might benefit the kidney in the immediate posttransplant period when it is susceptible to nephrotoxicity due to the damage from hypothermic storage.

Adult↗
PubMed1987

[Cytomegalovirus hyperimmunoglobulin prophylaxis following kidney transplantation. Results of a prospective randomized study].

The effectiveness of preventing cytomegalovirus (CMV) infections by administering CMV hyperimmunoglobulin was evaluated in a prospective randomized trial. The patients in the treatment group (n = 50) had intravenous infusions of 2 ml/kg bodyweight of CMV-Polyglobin at three-week intervals, up to day 105 after kidney transplantation. The 50 patients in the control group received no infusions. There was no significant difference between the treatment and control groups in transplant survival or patients survival rates. But the number of symptomatic CMV infections was higher in the control (n = 11) than the treatment group (n = 5). There were also significantly fewer symptomatic herpes-simplex infections in the treatment (n = 6) than in the control group (n = 25). It is concluded from these results that prophylaxis with CMV hyperimmunoglobulin should be undertaken either selectively or for shorter periods than those chosen for the reported trial.

Adult↗
PubMed1975

[Occlusion of sinus sagittalis superior by infiltration of a tumor metastasis (author's transl)].

As a casuistic contribution to differential diagnosis of thrombosis of cerebral veins and sinuses a case of occlusion of sinus sagittalis superior by infiltration of an intracerebral metastasis from a teratoma of testis is reported. The leading symptoms - epileptic seizures, progressive hemiplegia, choked papilla and clouding of consciousness - gave rise to the tentative diagnosis of a cerebral tumor; in carotis angiography however, the metastasis was not detected, merely the occlusion of the sinus was demonstrated. Therefore the progress of the syndrome was misinterpreted as caused by an advancement of a venous thrombosis. Only autopsy showed the symptomless primary tumor and its formation of metastases.

Adult↗