The June 2016 Compass

The June 2016 Compass opens with a report from Denny Flemming, who, prompted by Edgar Spencer, describes the impact IATDMCT has had in their laboratory in Velore, India. Denny has been featured in our June 2015 Blog and received praise in last month’s annual account, nevertheless her story is special and new details shine in this report. Denny describes collaborations that span France, Holland, Germany, the UK, the US and Australia. IATDMCT provided support for a National Symposium (India) on TDM in 2011 by sending four international experts. Later that year the group invited a member, Paul Taylor, met through IATDMCT, who helped to take the use of their recently acquired LC-MS/MS system to an expert level. The group was able to participate in a proficiency testing scheme in conjunction with Analytical Services International (ASI), where IATDMCT and ASI facilitates access by providing discounts to emerging countries. Subsequent research collaborations with members have led to successful publications, knowing members has helped apply new assays from published reports in conjunction with personal contact, and comparisons with others lets the group feel confident that they are providing a world class service. Currently they are looking at DBS analysis for affordable access to patients and to hospitals with limited resources. The report merits a read and Denny sums up with another adage, the Tamil proverb ‘Ottai pannaiyilum sakarai erukkum’ – ‘even a broken pot might contain sugar’; don’t disregard something because you don’t understand how useful it could be.

Amitava Dasgupta is an IATDMCT hero that I haven’t had the pleasure of meeting yet, although I regularly use a TDM textbook he has edited (in which many members feature as authors). Amitava shares a concise and complete account of urinary adulteration, the most common way to cheat a urinary drug test, profiling five methods and some possibilities to overcome them.

Marieke Sturkenboom and Daan Touw report of an unusual case of hypoglycaemia, reminding us of a common opportunity for a drug interaction, often designated as unlikely in interaction references. The group was able to unravel the mystery largely thanks to their ability to determine concentrations of both suspected drugs.

Debbie Marriot and Indy Sandaradura (on behalf of the Anti-infective Drugs committee) make a convincing case for fluconazole TDM, which is not typically considered a candidate due to its relatively stable PK profile and safety. Debbie presents in-house data, and three cases to illustrate that TDM would be highly useful in critically ill patients, especially those undergoing RRT or ECMO, or have especially high MICs. The data is unpublished, so you have all the more reason to refer to this great report.

The Immunosuppressive Drugs Committee do a great job summarizing developments surrounding Belatecept as an alternative immunosuppressant to CNIs in organ transplantation. They highlight important details of the trials, including important long-term success and safety profile. However, co-stimulation blockade-resistant rejection (CoBRR) may occur, particularly in the first-post transplant year, and is a challenge to manage and treat. Recent research of the immunological ballet involved is described, suggesting potential biomarkers, though we are still on new territory. I would like to acknowledge one of the authors, my good friend and colleague Dennis Hesselink, as the unofficial winner of the best dressed male at last year’s conference (judged by myself and colleagues from Limoges).

DBS is really making progress, largely thanks to pioneers from the clinical and university research arena, many of who are IATDMCT members. Elizabeth Berm and Jan Maring, on behalf of the Alternative Sampling Strategies Committee, report on the extension and exploration of analytical and clinical validation criteria for DBS in antidepressants, derived from simulation tests, to ensure confidence for clinically relevant interpretation of results, despite differences with plasma sampling.

Young scientist Fabienne Thomas, who won the best YS oral presentation at last year’s congress, presents the unfortunate case of patient’s death following 5-FU toxicity. Genotyping the three common polymorphisms in DPYD, known to affect function, was insufficient to explain the observed extremely low plasma dihydrouracil to uracil ratio (0.11). Exon sequencing revealed a previously unreported variant, an 8 bp duplication in exon 3, expected to result in a stop codon.

Finally, there is a also report by Franck Saint-Marcoux – who was lucky enough to go to DUPHAT, a spotlight on new members and our report about a year of blogging, and an invitation to the Kyoto 2017 Congress (the website is now live!). The 2017 Congress Organizing Committee is very happy to send promotional material and would appreciate support in spreading the word.

Intrigued? Read the Full reports in the June 2016 Compass.