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Daan Touw Q&A

At the IATDMCT Stuttgart congress in 2011 Pierre Marquet presented the results of an inquiry amongst members to describe their innovations/initiatives in TDM and Clinical Toxicology. The idea behind this blog is to showcase some of the initiatives presented there and to continue cataloguing the great things our members do.

The first interview was with Dan Touw, head of the clinical pharmaceutical and toxicological laboratory at the University Medical Center in Groningen. Dan uses dose adaptation software in clinical practice, and together with other colleagues, hosts an annual national training program for such software.

Could you tell us a little bit about your role as head clinical pharmaceutical and toxicological laboratory at the University Medical Center in Groningen? What is a typical day like for you?

My principal role is head of the laboratory. Our laboratory maintains pharmaceutical quality control of raw materials we purchase for the production of our own regular drugs and investigational drugs (IMP's) and the quality control of the drugs we have produced for our stock (EU-GMP regulations).

Further, we analyse samples for therapeutic drug monitoring (TDM) and clinical toxicology. Our laboratory has a 24-hours/day toxicological service. Besides these clinical tasks, our laboratory is involved in research. Examples of research projects are the development of new assays, the development of assays for recently developed drugs and the development of assays in alternative matrices such as hair and dried blood spots.

I’m also a hospital pharmacist consulting in our hospital for TDM, clinical toxicology and difficult clinical pharmacological cases. At the university I am a professor of bioanalysis, TDM and clinical toxicology, coaching PhD and masters students in their research.

A typical day starts with a short meeting to discuss what had passed the previous night, and the colleague on call reports his duties.

On Mondays I start with a staff meeting with my lab followed by a staff meeting with the pharmacy and pharmacology department. In the afternoon we have a short meeting with the department of pharmaceutical production where new studies and important projects with new IMP's and drug formulations are discussed. Then I supervise the trainees performing the TDM dose advice and advising on clinical toxicological issues. At the end of the day (after 18.00) I read my e-mails.

Tuesdays and Wednesday depend on my schedule, meetings with researchers, with representatives from companies, sometimes teaching, but always supervising our trainees in performing TDM.

Thursday is the day I do the routine TDM/toxicology activities in my lab, interpreting results and reporting them with dose advice.

Fridays are my faculty day. PhD and Masters students come to visit me for regular feedback. On Fridays the scientific meetings in the faculty of pharmaceutical sciences are scheduled, which I attend if possible.

One thing about your department I’ve admired is the use of MWPharm for dose adaptation as part of routine TDM. This program was developed in Groningen: I wonder if you might have been involved in the process of its evolution, and whether you might have some anecdotes to share?

I am involved in the testing of new versions. Unfortunately I have no anecdotes I can share. We use the software on a daily basis in forecasting drug levels and advising our doctors.

I understand that MWPharm is used in a number of centers around Holland. Was it difficult to achieve consensus and acceptance?

The program is 25 years old and increasingly being used. Kees Neef and I already have a history of 15 years of teaching our young colleagues and hospital pharmacy trainees (20 persons yearly) how to use MWPharm. This annual 2-day training session is held in a central place in our country with enough computers, and it is compulsory for hospital pharmacy trainees. Due to this teaching the use has been widespread and accepted in our country. Abroad MWPharm is hardly used, perhaps most in the Czech republic. Some colleagues in GB, Germany, France, Belgium, US use it.

There are some 180 drugs in MWPharm’s database: what are the clinical scenarios that you typically use it for?

MWPharm is most widely used for those drugs where TDM is indicated. Examples where we use MWPharm are the aminoglycosides, vancomycin, teicoplanin, HIV drugs, immunosuppressants, antifungal drugs, anti-TB drugs and I am sure that other users also use it for other types of drugs. In addition, MWPharm is also very useful for research purposes. It can also be used to build models for drugs.

Our practice is early limited sampling after the first dose. For example, a 90 year old patient with a creatinine of 100 micromole/L starts with 5 mg tobramycin per kg bodyweight. 1 hour after the first dose, a sample is drawn and a second sample at the next usual lab round. Since we do not perform trough/peak sampling at the second or third dose but immediately after the first dose, with 2 samples using MWPharm we can advise to adjust the dose before the second dose will be administered. 

Further, we use MWPharm in difficult cases of intoxications, to visualise the effect of dialysis on the levels and redosing, etc. MWPharm can be used for nearly every clinical question.

Another example is the question of compliance with antihypertensive drugs. A patient was suspected not to take his antihypertensive drugs and we measured the levels. Using his dosing schedule and average PK parameters we could prove that it was unlikely that he took his drugs regularly.

How does MWPharm incorporate into the workflow of a TDM request?

At this moment in the hospital where I work MWPharm is used by the staff of the lab. All drugs where a dose advice is needed, these cases are simulated in MWPharm and added to our database. The graphical output is poor we use the DOS-based program. With the analytical result a short written report about the pharmacokinetics (PK) in that patient and dose advice is put in the electronic records so the doctor can read our advice. In a hospital where I formerly worked I used to go to the ward with my analytical results and with the ward doctors around me I made the PK analysis and explained how I came to the advice.

As soon as a windows version is available, I can think of providing the graphical output to the doctor if he wishes.

Is there anything that your laboratory does or that is done at your hospital that you would consider innovative in terms of TDM and Clinical Toxicology?

We continuously develop new assays.  The latest developments are the new antifungal drugs and anti-tuberculosis (TBC) drugs. Another focus of our research is alternative sampling like dry blood spot sampling (in use for immunosuppressants, TBC drugs, antifungals, psychiatric drugs) and hair sampling (some 20 drugs of abuse).

Presently we are working on developing assays for tyrosine kinase inhibitors and monoclonal antibodies.

Concerning antibacterial drugs, we aim at optimising their use by measuring free drug levels in ICU patients because that is the active fraction.

Lastly, I have collected a large database of clinical PK cases (some 60.000). All patients are in MWPharm and we continuously develop PK models for different drugs and types of patients (adult, children, etc) and validate them based on this database.

Is there anything that you’ve seen elsewhere or heard about and thought “I’d like to incorporate that idea at my center”?

We do not perform pharmacogenetic analyses. Our laboratory does not have the facilities. I want to find a way to introduce this in our hospital.

At this moment we have an internet site and an intranet site. We have no newsletter to point to our new developments. I want to publish twice yearly a newsletter with relevant developments for interested laboratories.

The content of the IATDMCT Blog does not necessarily have the endorsement of the Association.