The possible pharmacokinetic interaction between the new immunosuppressive mycophenolate mofetil (MMF) and tacrolimus (TAC), respectively, was assessed by comparing routinely estimated mycophenolic acid (MPA) plasma trough levels of 15 consecutive renal transplant patients receiving MMF in combination with methylprednisolone (MEP) and cyclosporin A (CSA, 10 patients) or in combination with MEP and tacrolimus (TAC, 5 patients). Coadministration of TAC instead of CSA resulted in a significant increase of mean MPA plasma trough levels [3.4 +/- 1.3 microg/mL (n = 22) versus 1.87 +/- 1.1 microg/mL (n = 57); p < 0.001], despite lower MMF doses [1.5 +/- 0.5 g/d versus 1.7 +/- 0.3 g/d (not statistically significant)]. This elevation in MPA levels is possibly caused by an interaction between MMF and TAC and could lead to a recommendation to monitor MPA plasma levels with appropriate dose adjustment.

There has been limited experience with routine therapeutic monitoring of mycophenolic acid (MPA; CAS 24280-93-1), which is the active metabolite of the new immunosuppressive prodrug mycophenolate mofetil (MMF; CAS 115007-34-6). MMF was introduced with recommendation for fixed oral dosing (1 g twice daily) in combination with cyclosporin A (CSA) and a glucocorticoid for the prevention of renal allograft rejection. In the course of routine CSA monitoring a MPA monitoring was performed in adult renal transplant patients receiving MMF in combination with CSA and methylprednisolone (MEP). For 30 consecutive patients with 234 plasma samples the relationship of MMF doses used and MPA plasma through levels estimated at steady state (C88 min) to clinical outcome was evaluated retrospectively. The MPA concentrations were determined with the enzyme-multiplied immunoassay technique (EMIT mycophenolic acid assay) on a Cobas Mira Plus analyzer. The within-run (n = 10) and between-run (n = 10) coefficients of variation were 3.6%, 3.5%, 3.1% and 3.6%, 5.1%, 6.7% analysing three MPA level plasma controls (1.25 mg/l, 7.5 mg/l, 12.5 mg/l), respectively. The data analysis of the MPA plasma trough levels resulted in a high variability between patients (0.3 to 3.4 mg/l) received the recommended fixed MMF dose (2 g/day). There was a higher incidence of adverse reactions with increasing MPA plasma trough levels (2.13 +/- 1.35 mg/l in 13 patients with side effects versus 1.53 +/- 0.67 mg/l in 17 patients without side effects; p < 0.001), regardless of reduction of MMF dose (1.77 +/- 0.3 g/day versus 1.89 +/- 0.2 g/day; NS), respectively. No acute rejection episodes occured under MMF administration in combination with CSA and MEP. The study shows that the to date recommended MMF dose resulted in individual, quite different MPA plasma trough levels, which were associated with incidence of side effects rather than the MMF doses. Therefore, monitoring of plasma MPA trough levels and individual dose adjustment could be helpful to reduce the incidence of adverse reactions and to increase the safety of MMF therapy.

Nesidioblastosis pancreas was used as an immunogen in BALB/c-mice to generate monoclonal antibodies against structures of human islet cells. Seven clones were selected by screening 311 growing hybridomas for reactivity with the rat insulinoma cell line, RIN m5F, and with cryostat sections from human pancreas. None of the selected clones reacted with pancreatic hormones or endocrine-specific peptides. Monoclonal antibodies cross-reacting with the RIN-cell line also bound to different endocrine organs or cell lines, while some RIN-cell-negative clones bound only to Langerhans islets from human pancreas.

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