Cinacalcet's effect on the pharmacokinetics of tacrolimus, cyclosporine and mycophenolate in renal transplant recipients.

Background: The calcimimetic drug cinacalcet offers a novel therapeutic option to treat post-transplant hypercalcemia and hyperparathyroidism; however, the interaction with calcineurin inhibitors and mycophenolate has not been evaluated.

Methods: In the present study the effects of cinacalcet on the pharmacokinetics of cyclosporine A (CsA), tacrolimus (Tac) and mycophenolate were investigated in 14 renal transplant recipients with stable renal function (mean creatinine 126.4 +/- 45.

Determination of ciclosporin A and its six main metabolites in isolated T-lymphocytes and whole blood using liquid chromatography-tandem mass spectrometry.

A specific and sensitive method for determination of intracellular ciclosporin A (CsA) and its six main metabolites AM1, AM9, AM1c, AM1c9, AM19 and AM4N, in isolated T-lymphocytes and whole blood is described. T-lymphocytes were separated from whole blood using Prepacyte. The analytes were extracted and purified from isolated lymphocytes and whole blood by protein precipitation followed by solid-phase extraction (SPE).

Atorvastatin does not affect the pharmacokinetics of cyclosporine in renal transplant recipients.

Objective: The aim of the present study was to evaluate the possible influence of atorvastatin on the pharmacokinetics of cyclosporine (INN ciclosporin) and its main metabolites, AM1 and AM9, in renal transplant recipients.

Methods: Whole blood samples from 18 renal transplanted patients on cyclosporine-based immunosuppressive therapy were collected prior to and after 4 weeks of treatment with atorvastatin (10 mg/day) and analysed with regard to both cyclosporine and its main metabolites, AM1 and AM9, using a specific chromatographic method with ultraviolet detection.

Results: On average, AUC(0-12) [area under the whole blood concentration versus time curve in the dosing interval (0-12 h)] of cyclosporine was 5% (-16, 5) (90% confidence interval) lower upon co-administration with atorvastatin.

Screening for central nervous system-stimulating drugs in human plasma by liquid chromatography with mass spectrometric detection.

Liquid chromatography and electrospray mass spectrometry was evaluated for screening of more than 70 central nervous system-stimulating drugs in human plasma. Protein precipitation was utilized as a simple sample preparation procedure, and the subsequent screening procedure involved two injections in a liquid chromatography-mass spectrometry system for each sample; a first screening without source induced dissociation to maximize sensitivity where potential positive identifications were based on retention time and molecular ion masses, and secondly a source induced dissociation confirmation based on retention time, molecular ions, and one or two fragment ions for each target generated by a 25 V fragmentation energy. The majority of central nerve system stimulating drugs were possible to identify within the actual therapeutic ranges.