Application of an isocratic methanol-based HPLC method for the determination of iohexol concentrations and glomerular filtration rate in patients with cirrhosis.

BACKGROUND: Glomerular filtration rate (GFR) and mortality is more accurately determined by gold standard measures than serum creatinine-based estimates in cirrhosis. No formal validation of any gold standard method has been reported. METHODS: An isocratic methanol-based method incorporating the reference standard iohexol-related compound C was developed and validated in 12 patients with cirrhosis by simultaneously determining GFR using iohexol and chromium-51 labelled ethylenediamine tetraacetic acid ((51)Cr-EDTA) clearance. Iohexol pharmacokinetics was also studied with the collection of blood and ascitic fluid at intervals following an iohexol bolus. RESULTS: Triplicate assays produced a linear calibration curve (R (2)=0.99, N=5) over an iohexol concentration range of 23.6-755 µg/L. Mean (range) extraction recovery of iohexol from serum was greater than 95% (94-97%), with an intra-day coefficient of variation less than 3%. Twelve patients with cirrhosis with mean Child-Pugh score of 9 displayed a mean difference (bias) -1.3 mL/min/1.73 m(2) (-18 to +16) comparing iohexol with (51)Cr-EDTA. Iohexol equilibrated between blood and ascitic compartments after 4 h. CONCLUSION: A simple, cheap, and accurate isocratic, methanol-based method for the determination of iohexol concentrations is described, validated according to Food and Drug Administration guidance. Iohexol demonstrated comparable performance with (51)Cr-EDTA in determining GFR. Delayed equilibrium of iohexol between blood and ascitic compartments suggests sampling beyond 4 h would improve accuracy of GFR determinations in patients with cirrhosis.

Current status of immunosuppressive agents for solid organ transplantation in children.

Immunosuppression after organ transplantation is complex and ever evolving. Over the past two decades, newer immunosuppressive agents have been introduced with an aim to provide better patient and graft survival. Improved therapeutic strategies have been developed offering the option to use combinations of drugs with non-overlapping toxicities. There are, however, only a few clinical studies with robust data to rationalize the use of these agents in children. This review will discuss the newer immunosuppressive agents used for solid organ transplant, their current status in post-transplant management and prevention of allograft rejection.

Consensus report on therapeutic drug monitoring of mycophenolic acid in solid organ transplantation.

With the increasing use of mycophenolic acid (MPA) in solid organ transplantation, the need for more accurate drug dosing has become evident. Personalized immunosuppressive therapy requires better strategies for avoidance of drug-related toxicity while maintaining efficacy. Few studies have assessed the clinical usefulness of therapeutic drug monitoring (TDM) of MPA in solid organ transplantation in a prospective way, and they have produced opposing results. To provide clinicians with an objective and balanced clinical interpretation of the current scientific evidence on TDM of MPA, a consensus meeting involving 47 experts from around the world was commissioned by The Transplantation Society and held in Rome on November 20 to 21, 2008. The goal of this consensus meeting was to offer information to transplant practitioners on clinically relevant pharmacokinetic characteristics of MPA, to rationalize the basis for currently advised target exposure ranges for MPA in various types of organ transplantation, and to summarize available methods for application of MPA TDM in clinical practice. Although this consensus report does not evaluate the final role of MPA TDM in transplantation, it seeks to examine the current scientific evidence for concentration-controlled dosing of MPA.