Clin Pharmacokinet
-
Clinical Trial
Effect of severe renal failure and haemodialysis on the pharmacokinetics of levosimendan and its metabolites.
Levosimendan is a calcium sensitiser developed for the treatment of congestive heart failure. It increases myocardial contractility, reduces the filling pressure and dilates both the peripheral and coronary vessels. The circulating metabolites of levosimendan, OR-1855 and OR-1896, are formed and eliminated slowly after intravenous administration of levosimendan. The aim of this study was to investigate the effect of impaired renal function and haemodialysis on the pharmacokinetics of levosimendan, OR-1855 and OR-1896. ⋯ The t(1/2) of the levosimendan metabolites was prolonged 1.5-fold and their AUC and C(max) were 2-fold in patients with severe CRF and ESRD patients undergoing haemodialysis as compared with healthy subjects. These results suggest that the dose should be reduced when levosimendan is used for the treatment of congestive heart failure in patients with severe renal insufficiency.
-
Comparative Study Clinical Trial
Pharmacokinetics of mycophenolic acid and determination of area under the curve by abbreviated sampling strategy in Chinese liver transplant recipients.
This study aimed to: (i) define the clinical pharmacokinetics of mycophenolic acid (MPA) in Chinese liver transplant recipients; and (ii) develop a regression model best fitted for the prediction of MPA area under the plasma concentration-time curve from 0 to 12 hours (AUC(12)) by abbreviated sampling strategy. ⋯ This study showed the wide variability in MPA AUC(12) in Chinese liver transplant recipients. Single timepoint MPA concentration during the 12-hour dosing interval cannot reflect MPA AUC(12). MPA AUC(12) could be predicted accurately using 1, 2, 6 and 8 hour timepoint MPA concentrations by abbreviated sampling strategy.
-
The FG loop peptide (FGL(L)), a novel mimetic of the neural cell adhesion molecule (NCAM), is in clinical development for neurodegenerative disorders such as Alzheimer's disease. Preclinical studies in rats, dogs and monkeys have demonstrated exposure in plasma and cerebrospinal fluid after parenteral or intranasal administration of FGL(L), with no systemic toxicity. This article reports on the results of the first administration of FGL(L) in humans. ⋯ Intranasal administration of FGL(L) (25, 100 and 200mg) was well tolerated in healthy male volunteers, with no safety concerns and a pharmacokinetic profile that was generally dose related. Further studies are currently being planned to evaluate the effects of FGL(L) in patients with Alzheimer's disease.