Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A major factor influencing whole blood cyclosporin A levels in young children with renal transplants is the variable absorption of Sandimmun (SIM). Neoral (NEO) is a new microemulsion of cyclosporin A (CYA) that has been reported to have better absorption characteristics. We compared the pharmacokinetics of SIM and NEO in nine renal transplant recipients aged less than 11 years (range 4.8-10.9 years) and observed clinical parameters during 6 months of NEO therapy. Median CYA dosage was 149 mg/m2 per day (range 98-226). We observed an increase in the maximum CYA concentration (Cmax) of 114%, an increase in area under the curve (AUC) of 71% and the time to reach Cmax was reduced from 1.75 h to 1.25 h with NEO, while 12-h trough levels (C12 h) did not change significantly. AUC correlated with C12 h for SIM (r2 = 0.833) and NEO (r2 = 0.699) and also C1.5 h for NEO (r2 = 0.775). During 24 weeks' follow-up, the coefficient of variation of CYA levels was lower for NEO (13%) than for SIM (20%). Although CYA dosages at the start and the end of 6 months on NEO were similar, only one patient was maintained on a constant dose. Four patients had acute reversible rises in plasma creatinine which responded to a 11% reduction in NEO dose; their increase in AUC was greater than those patients not showing a rise in plasma creatinine. Overall, median plasma creatinine was unchanged at the end of the study. NEO was well tolerated by the patients; temporary nausea and headache were experienced by three patients and one of them stopped NEO after 20 days. Other biochemical parameters were not significantly different on NEO.
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PMID:Comparison of Neoral and Sandimmun cyclosporin A pharmacokinetic profiles in young renal transplant recipients. 920 80

Neoral is a new formulation of cyclosporine based on microemulsion technology, designed to provide increased and more reliable absorption of the medication. The aim of this study was to assess whether conversion from Sandimmune to Neoral provides safe and effective oral immunosuppression in stable liver transplant recipients. We studied 59 stable liver transplant recipients (being treated with prednisone, azathioprine, and Sandimmune). All patients were enrolled in an open-label study in which they were converted from Sandimmune to Neoral therapy at a dose ratio of 1:1. Thirty-nine patients underwent duct-to-duct bile duct anastomoses, and 20 underwent Roux-en-Y bile duct anastomoses. After conversion, the Neoral dosage was adjusted on the basis of trough levels measured at weeks 1, 2, 3, 4, 6, 8, and 12. To assess safety and tolerability, we prospectively obtained serial information, including laboratory data and information on side effects. Standard statistical methodology was used. A total of 59 patients (23 men, 36 women; mean age, 55 years; mean follow-up after liver transplantation, 5.7 years) completed 3 months of follow-up after conversion from Sandimmune to Neoral. There were 32 dosage changes; 22 (69%) required reduction of the Neoral dose. Mean cyclosporine trough levels remained above 100 ng/mL during the follow-up period. There were no significant differences between cyclosporine levels in patients with duct-to-duct or Roux-en-Y bile duct anastomoses. There were no episodes of rejection during the 3-month follow-up period. The side effect profile was similar in both groups, except for a significant reduction in the number of patients with headaches after Neoral conversion. Liver transplant recipients can safely be converted from Sandimmune to Neoral. Neoral was well tolerated in this population.
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PMID:An open-label study of the safety and tolerability of converting stable liver transplant recipients to neoral. 972 79

Neoral is a microemulsion formulation of cyclosporin (CyA), which has more consistent and better pharmacokinetics parameters with improved bioavailability compared to conversional formulation of Sandimmune. Sixty-four stable adults (age >18 years), who had received liver transplants (LTx) and were on Sandimmune-based immunosuppression, were converted to Neoral on milligram for milligram basis. Mean age was 52.5 +/- 13.5 years and male/female distribution was 22/42. Mean interval from LTx to conversion was 109.2 +/- 136 months. In 13 patients (20%) the dose of Neoral was reduced because of an increase in serum creatinine (N = 9), hyperkalemia (N = 1), headache (N = 1), peripheral parasthesia (N = 1), and a general sense of discomfort (N = 1). Interestingly, in two patients a decrease in the trough concentration was observed with the increase in liver enzymes. Both patients responded to an increase in Neoral dose. The present study suggests while the majority of the stable liver transplant patients (77%) can be safely converted to Neoral from Sandimmune on a milligram to milligram basis, they need to be carefully monitored for renal function, liver function, and trough concentration of CyA.
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PMID:A prospective study on conversion from sandimmune to neoral in stable adult liver transplant recipients. 1021 37

Neoral is a new formulation of cyclosporine that permits reliable absorption in patients with external biliary drainage. The authors reviewed 227 liver transplant patients receiving primary treatment with Neoral. Headache occurred in 24 patients (11%), mild tremors in 12 patients, paresthesia in 5 patients, acute confusional state in 4 patients, and seizures in 2 patients. It is apparent that Neoral has profoundly reduced the severity of neurotoxicity in liver transplant recipients.
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PMID:Oral cyclosporine decreases severity of neurotoxicity in liver transplant recipients. 1033 8

The aim was to study the ursodeoxycholic acid (UDC) effect on the cyclosporin A (CsA) pharmacokinetics after oral administration of the microemulsion formulation Neoral (CsA-ME) in liver transplant recipients, and test the potential protective effect of this bile acid on liver and renal CsA-ME-induced toxicity. At entry into the study, 12 patients who underwent orthotopic liver transplantation received CsA-ME, for at least 6 months. They then received a cotreatment CsA-ME plus UDC (13.8 mg x kg(-1) x day(-1)) for three months. Blood concentrations of CsA were measured using a monoclonal antibody specific for the parent compound. The kinetic data were analysed by a mathematical model incorporating a time dependent rate coefficient for CsA intestinal absorption, before and after UDC treatment. Changes in serum markers of hepatic and renal injury were assessed. Individual serum bile acids were determined by chromatography. Serum levels of UDC increased from 3 to about 45% of total serum bile acids after UDC treatment. The estimated model parameters indicate that UDC administration modulates CsA intestinal absorption. In the nine non-cholestatic patients, UDC reduced the absorption rate and the bioavailability of CsA without modifying the elimination rate constant of CsA and the CsA pre-drug levels. In contrast, in the three cholestatic patients, the bioavailability tended to be higher and the absorption rate faster when CsA was combined with UDC. UDC significantly decreased elevated gamma-glutamyl transferase and creatinine serum levels and induced some clinical improvements such as disappearance of headaches in four patients. In conclusion, a 3-month UDC treatment modifies CsA intestinal absorption without affecting CsA elimination rate constant. On the other hand, UDC supplementation appears to improve CsA tolerability.
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PMID:Ursodeoxycholic acid modulates cyclosporin A oral absorption in liver transplant recipients. 1120 11

Cyclosporine (CyA) trough concentrations are poor predictors for acute rejection post-transplant. Patients were part of a randomized trial of basiliximab (n=70) vs. anti-thymocyte globulin (ATGAM) (n=65), both in combination with Neoral, mycophenolate mofetil, and steroids, undergoing first or second, cadaveric or live donor renal transplants. Whole blood samples were collected just before (C0) and at 2 h after CyA dosing on day 4 and at the end of weeks 1, 2, 4, and 8. The CyA was measured by fluorescence polarization immunoassay (TDx). Mean CyA C0 and C2 concentrations were calculated. Logistic regression analysis revealed that mean C2 level was the only predictor of acute rejection (P < or = 0.001). Higher mean C2 levels predicted lower rejection probabilities. Linear regression analysis revealed that higher mean C2 levels were not related to higher serum creatinine levels at either week 4 or 24 or to incidence of headache or tremor. The CyA C2 levels predict the frequency of rejection postrenal transplant. Target C2 levels are in the range of 1500 ng/dL.
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PMID:Two-hour post-dose cyclosporine level is a better predictor than trough level of acute rejection of renal allografts. 1222 36