Published by: michadmin on May 28th, 2012
My career research focus has been the study of drug disposition and effects at extremes of age. I have had the opportunity to participate in pediatric research studies since the early 1970’s when I was on staff in the Division of Clinical Pharmacology at McGill University. I developed one of the early HPLC assays for theophylline at a time when its use as a therapeutic agent was quite controversial. Our research team went on to use this technology to develop dosage strategies for the use of intravenous theophylline to manage human apnea of prematurity, and to delineate a therapeutics strategy for this drug in the management of asthma symptoms in children. Concurrently, we were able to study the disposition of propylthiouracil in pregnant hyperthyroid women at various stages of pregnancy and its placental transfer and potential impact on thyroid function in the neonate. Finally, our research team was able to determine pharmacokinetic-pharmacodynamic relationships of the diuretic furosemide in neonatal patients with high output cardiac failure. All of these findings have been published in the peer-reviewed literature. This was an exciting time to be able to study the use of drugs in critical health problems of the neonate and in young pediatric patients.
In 1978, I was recruited back to the Faculty of Medicine at the University of Manitoba to the Section of Clinical Pharmacology. While re-establishing my overall research program, my focus on pediatric research turned to the use of animal models to investigate significant issues in the use of anesthetics during birth, and problems related to the consumption of ethanol by pregnant females and its impact on autoregulation of cerebral blood flow in the neonate. These animal studies were completed primarily in partnership with colleagues in the Department of Anesthesia. In the midst of these animal studies I was introduced to Dr. Milton Tenenbein of the Department of Pediatrics. We developed a long-standing partnership that used human research volunteers and resulted in significant contributions to the scientific literature focused on assessment of efficacy of decontamination strategies for pediatric patients with drug overdoses. It was during this time that we originated the successful therapeutic intervention of orogastric lavage to manage overdoses with modified-release drug dosage forms.
Most recently, I have had the opportunity to collaborate with other centres to address additional issues related to child health. A recently published study addressed ethical dilemmas in the use of pediatric persons as research subjects. This was an international study that compared and contrasted analogous issues between investigators in the United Kingdom and Canada. With respect to neonatal health, I have been fortunate to collaborate with a colleague in Alberta to use studies in animal models of pregnancy to successfully dissociate the adverse health effects of smoking in pregnancy from those of nicotine alone. These preclinical studies provide a basis for clinical trials to determine whether provision of nicotine substitution to smoking mothers during pregnancy might provide an acceptable harm reduction strategy to the developing fetus and neonate.