No abstract

No abstract

The riparian brush rabbit (Sylvilagus bachmani riparius) is an endangered species found in dense, brushy habitat in the California's Central Valley. We implemented a reintroduction program to bolster populations at a Federal Wildlife Refuge and to assess factors influencing mortality and subsequent survival of released individuals. Between July 2002 and July 2005, we reintroduced 325 captive-bred individuals to unoccupied habitat within their historic range using a soft-release strategy and monitored their subsequent survival with radiotelemetry. Longer time in soft-release pens resulted in increased monthly survival. Rabbits were most susceptible to post-release mortality during the first 4 weeks following reintroduction and both body mass and length of time in the soft-release enclosure influenced this relationship. When we controlled for release mortality during this acclimation period, subsequent monthly survival probabilities were most strongly influenced by release year (year 1 vs. years 2 and 3) and by a catastrophic flooding event; length of time in the soft-release enclosure remained an important variable in longer-term survival. Cause of mortality was unknown for the majority of deaths (61.9%), but predation (including presumptive predation) was the greatest known cause of death in translocated rabbits (26.4%). Reintroduction programs should employ an adaptive management approach with ongoing monitoring of target animals and concurrent analysis to allow managers to adjust methods as conditions dictate.

No abstract

Pharmacokinetic concepts provide a basis for individualization of drug therapy to optimize outcomes of the critical-dose drugs cyclosporine (CsA), tacrolimus (TRL), sirolimus (SRL), and mycophenolate mofetil (MMF). The therapeutic range of a drug-defined as the concentrations at which the desired pharmacologic effect is produced without adverse effects in most patients-is difficult to achieve given the significant inter-and intrapatient variability of the effects of a given concentration of therapeutic agents. Because of the highly variable rates of absorption of immunosuppressive agents and clinical responses to given concentrations in transplant recipients, individualization of drug regimens by using therapeutic drug monitoring (TDM) is essential to optimize pharmacotherapy Assessing proclivity for acute rejection episodes in transplant recipients currently is attempted by estimating drug exposure using the area under the time-concentration curve (AUC) for MMF and the average concentration (Cav, the quotient of the AUC and the dosing interval) for CsA. These studies have revealed that low oral bioavailability was a more important predictor of rejection than was a rapid clearance rate. In addition, the degree of intra-individual variability of AUC values correlated with the development of chronic rejection in renal transplant recipients. Similarly, TDM of MMF requires AUC determinations. Low mycophenolic acid (MPA) exposure, as estimated by the AUC, demonstrates a significant association with an increased risk of an acute renal transplant rejection episode. The AUC0-2 estimate of MPA shows good agreement with the 12-hr AUC estimate from samples obtained during the entire dosing interval. In contrast, trough levels are utilized during treatment with TRL or SRL, potent new immunosuppressive agents that display a pleiotropic array of side effects. Standard body measures, including weight and body mass index, poorly predict the concentration of SRL in whole blood. Large inter- and intra-individual differences displayed in patients also could not be predicted by demographic features or by laboratory parameters. When SRL is given with other immunosuppressive agents such as CsA, which shares with SRL mutual microsomal metabolism by the cytochrome P450 3A system, pharmacokinetic interactions occur, especially when the agents are administered concomitantly. Because of the critical-dose nature of most of the recent generation of immunosuppressive agents, therapeutic drug monitoring is becoming increasingly important in the selection of doses and treatment regimens.