Our second blog interview is with Paula Schaiquevich, CONICET researcher at the Paediatric Hospital Dr. Juan P Garrahan in Buenos Aires, Argentina. Paula’s research work involves pharmacokinetic/ pharmacodynamic studies of chemotherapy and development of new routes/new drugs for patients with retinoblastoma.
You are a researcher and you also work in the lab at the Children’s hospital (Hospital de Pediatria JP Garrahan). Can you tell us a little bit about your respective roles? What is a typical day like for you?
Yes, I am a researcher at CONICET, the main national organization for research and development of technology in Argentina. In my country, researchers are financed by the state for doing research. We have a research career stream, in which you have to qualify with the requisites to achieve a position and keep ascending within the system.
For CONICET my line of research concerns pharmacokinetic/ pharmacodynamic studies of chemotherapy and development of new routes/new drugs for patients with retinoblastoma. As my lab is inside a hospital I also participate in various other projects related to TDM: development of new analytical techniques for specific research projects; pharmacovigilance and pharmacokinetics of immunosuppressants and antibiotics in pediatrics.
It is quite difficult to describe a “typical” day in the lab because regardless of how I plan it, I always have unplanned tasks (including administrative tasks). Some days I advocate within the animal facility on matters related to research involving animals (inside the same hospital), other days I write grants, manuscripts, submission for fellowships for the PhD students that work with me, or be called to advise on vancomycin dosing, for example, at the hospital.
I’ve always been impressed hearing about your work related to the PK of topotecan in intraocular injections for retinoblastoma. It is a story that extends over quite a period, and the continued research by yourself and your co-workers continue to bring new insights about the best ways to treat the condition. It is also an impressive story of collaboration and of translational medicine. Can you take us through the story?
When I returned to Argentina from the USA, following my postdoc at St Jude Children’s Research Hospital, I joined the research group in retinoblastoma at Hospital Garrahan. This group had already been working in new routes of chemotherapy delivery and schedules of treatment for retinoblastoma patients. Our research is based on finding new drugs or indications for refractory/relapsed patients, and new routes for chemotherapy delivery in order to increase the bioavailability in ocular structures affected by tumor.
My contribution was establishing a technique for directly injecting chemotherapy in the ophthalmic artery of an animal model (the pig), with the aim to translate this technique to humans. It was the first time the technique was developed Latin America, and we are the only group to perform pharmacokinetic studies in animals and patients after the administration of drugs using this technique. I must add that it is not the result of my personal work, but that of our group (we are more than 10, including a neurointerventionist, veterinarians, biochemists, an oncologist, an ophthalmologist and nurses).
After having studied about 30 patients and more than 70 cycles of chemotherapy, we found that increasing the dosage of some chemotherapeutic agents mainly lead to severe neutropenia. In addition, we observed that combining different agents showed synergistic effects in vitro in retinoblastoma cell lines. Thus, we recommended lowering the dose and administer the combination.
Thereafter, we investigated other routes of chemotherapy delivery, including intravitreal injection and always, characterizing the pharmacokinetics of the drug delivered by the studied route. We continue our work and now, we are also studying the effect of drugs that are already on the market but could potentially be used in retinoblastoma as a novel indication.
Do you have any anecdotes about the experience?
I have thousands of anecdotes: actually that’s what Argentineans are known for!
One example: when I started the development of the super-selective ophthalmic artery infusion in pigs, about 2 weeks after I received the pigs to the animal facility, the swine flu broke out worldwide and I was required to stop the experiments. Some circumstances are tragicomic, as you want to cry but finally, you have to laugh!
What are some innovative things you do in pharmacology at the clinical chemistry laboratory at your hospital?
As I said before, we develop new routes for chemotherapy delivery. We are a strong group in evaluating ocular and systemic toxicity in animals after different treatments.
I have started a line of research identifying new drugs and evaluating different drug combinations and schedules of treatment based on cytotoxicity studies in tumor cells. Other research line is our collaboration with the Pharmaceutical department at the University of Buenos Aires in which we work on pharmaceutical forms for sustained chemotherapy delivery for ocular tumors.
Besides these examples, we work on population pharmacokinetics of antibiotics for routine TDM. Mainly, we work on vancomycin in neonates, cystic fibrosis and pediatric transplant patients. This work is mainly carried out by my colleague Paulo Caceres Guido. We have started a project concerning the pharmacokinetics/ pharmacodynamics of calcineurin inhibitors in renal and liver pediatric transplant.
We’ve received much intellectual support from Dr Pierre Marquet, Dr Roger Jelliffe and Dr Michael Neely. They all support our research projects and provide good advice. We also appreciate Dr VanGelder’s support and this year one of our PhD students will spend some months at his hospital (2014).
I remember hearing about the challenges you’ve faced at your centre in the switch to generic immunosuppressant drugs in pediatric patients. What were the challenges, and how did you manage to resolve the issues?
Well, sometimes science is close to politics and we have to know how to deal with these situations. We have something in mind and it’s that we work based on science, thus the result is the result, and we publish what the “numbers” say. Then, we have to work out the best scenario to translate it into the clinics.
Interestingly, we (including Paulo) have achieved a very productive group including pharmacists from our hospital, physicians, transplantologists, and have established a collaboration with the National Institute of Transplant and Procurement (INCUCAI). Under this collaboration, we started different training in this area (what TDM means and involves, how and when to perform the analytical assays for TDM, aspects of pharmacovigilance) including a symposium that was held in November 2013. For the current year (2014), we are planning to provide training in different provinces of the country. We are convinced that good science and education is the basis for good clinics.
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