Evaluation of inosin-5'-monophosphate dehydrogenase activity during maintenance therapy with tacrolimus

Objectives: The aim of this study was to identify a target range for inosin‐5′‐monophosphate dehydrogenase (IMPDH) activity in maintenance therapy with tacrolimus (TCL), and to apply the measurement of IMPDH activity to the therapeutic drug monitoring for mycophenolate mofetil (MMF). Methods: Eleven patients with renal transplants and 10 healthy volunteers were investigated. All patients were treated with a combination of TCL, steroid and MMF for 2 months after transplantation, and were in stable and good condition. IMPDH activity was determined indirectly by measuring xanthosine 5′‐monophophate in cell lysates supplemented with IMP and β‐nicotine adenine dinucleotide using an high‐performance liquid chromatography (HPLC) method. Results: The within‐run reproducibility of the assay was excellent, with relative standard deviation (RSD) values of 0·41–4·08%. The mean differences between the spiked concentrations of xanthosine 5′‐monophophate and their real values (mean relative errors; MREs) were within a range of 2·66–8·89%, showing good accuracy. The interday RSD values were 1·51–6·12% and MREs ranged from 2·10% to 8·89%. Cell lysates showed a 5–6 nmol/L IC₅₀ mycophenolic acid (MPA) concentration. TCL, cyclosporine and prednisolone did not affect IMPDH activity. The peak MPA concentration was achieved at 1 h after dosing. IMPDH activity decreased to 75% and 67% at 1 and 2 h after dosing respectively. Therefore, the inhibition rates of MPA against IMPDH activity may be adequate at 25–40% in TCL maintenance therapy. Conclusion: Inosin‐5′‐monophosphate dehydrogenase activity in cell lysates could be reliably determined by HPLC. A 25–40% inhibition of IMPDH activity may be an appropriate range for preventing rejection with MPF but this requires further validation using larger studies with harder outcomes such as rejection episodes.     

Harm Reduction Behaviors Among Young Polysubstance Users at Raves

ABSTRACT. Background: Raves may be considered recreational settings in which drug use and health risks related to polydrug use are higher than in others. Harm reduction behaviors implemented by ravers are of particular relevance in reducing such risks. This study analyzes harm reduction behaviors and their relationship to raver polysubstance use patterns. Methods: Cross-sectional study of 248 ravers recruited at underground raves in Andalusia (Spain). A questionnaire was developed to collect information about their sociodemographics, drug use, and harm reduction behaviors. Results: The results show that ravers employ harm reduction behaviors for minimizing drug-related harm. Nevertheless, only a small minority of the participants frequently employed harm reduction behavior for polysubstance use as well. Ravers identified as high polysubstance users protected themselves significantly less than those identified as low polysubstance users. Conclusions: This study provides empirical information that may be useful for harm reduction intervention in a hidden and hard-to-reach population like rave attendees. The results point to the need to inform and increase harm reduction behavior specifically aimed at polysubstance use by ravers, especially among more frequent users. Future directions for research are also suggested.