Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 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

A 58-year-old man with end-stage renal failure secondary to polycystic kidney disease developed a profoundly elevated mycophenolic acid (MPA) free fraction and associated severe toxicity after cadaveric renal transplantation. Initial immunosuppressive therapy was 4 mg/kg body weight bid cyclosporin (Neoral; Novartis Pharmaceutical Co Ltd, Sydney, Australia) given orally with 1 g bid mycophenolate mofetil (MMF) (CellCept; Roche Products Pty Ltd, Sydney, Australia). In the first 5 days posttransplantation, the serum creatinine concentration fell, and the patient developed profound hypoalbuminemia (serum albumin <20 g/L) and hyperbilirubinemia (serum bilirubin >150 micromol/L) that resulted from progressing biliary obstruction. On day 5 posttransplantation, the 2-hour whole-blood cyclosporin concentration and total MPA area under the curve (AUC(0-6)) were low (837 microg/L and 12.6 mg x h/L, respectively), while the total mycophenolic acid glucuronide (MPAG) AUC(0-6) was elevated (1317 mg x h/L). MMF was continued at the same dose, but tacrolimus substituted for cyclosporin. The patient subsequently experienced severe nausea, vomiting, hematemesis, and pancytopenia (nadir white cell count 1.6 x 10(9)/L, platelet count 32 x 10(9)/L, and hemoglobin 73 g/L) that were normalized after cessation of MMF. Retrospective measurement of the free MPA concentration on day 5 showed that free MPA AUC(0-6) was markedly elevated at 2.3 mg x h/L, as was the free fraction, at 18.3%. This case illustrates how altered protein binding can be associated with severe MMF toxicity caused by an increased free MPA concentration despite relatively low total MPA. These data support the monitoring of free MPA concentrations in those patients considered at risk for MMF-related toxicity.
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PMID:Severe toxicity associated with a markedly elevated mycophenolic acid free fraction in a renal transplant recipient. 1525 77