What does the human body do with the medications and drug therapies it ingests? How does underdosing or overdosing affect clinical outcomes? Rambam Health Care Campus (Rambam), in Haifa, Israel is now offering a service that personalizes drug doses to each patient’s specific needs.
Precision and individualized medicine are influencing the future of healthcare. Administering a precise and effective dosage in adult patients comes with challenges – but in infants and toddlers, the problem and risks are more significant.
One of a physician’s many challenges is adjusting and fine-tuning a patient’s drug dosage according to the patient’s individualized needs. Overdosing or underdosing can have severe consequences and even be life-threatening. Rambam is implementing a relatively new medical specialty – pharmacokinetics (PK) to overcome the obstacles associated with administering incorrect doses of medication and drug therapies.
“Pharmacokinetics is a branch of pharmacology that studies the body’s interaction with administered substances over time,” explains Professor Daniel Kurnick, director of Rambam’s Clinical Pharmacology Institute, “On a global scale, we are seeing how outdated practices of administering the same fixed dose to all patients is giving way to new approaches.”
Existing methods of determining the optimal dose for each patient are fraught with difficulties, especially in infants and toddlers. Medication adjustment methods are based on the patient’s body weight and size. Yet, they do not consider other differences: the body’s ability to eliminate drugs, gender, genetic variables, and more. Therefore, despite adjustments made based on body weight and size, significant variations are noticed in a patient’s blood samples. Varying drug concentrations in the blood affect a drug’s potency, effectiveness, and the presence and intensity of side effects.
“We measure drug concentrations in the blood. Based on these results and our understanding of the effects of the drug on each patient, the dosage can be adjusted and personalized during the treatment cycle,” Professor Kurnick continues, “For example, in patients with diabetes and high blood pressure, in whom the maximum effect of the drug builds up over time, we can start with a low dose and steadily increase or decrease the dosage according to the patient’s response.”
What happens when there is a need to achieve maximum effectiveness immediately upon commencing treatment? Antibiotics and chemotherapies are two examples. In these cases, physicians must endeavor to fine-tune drug dosage as soon as possible. Rambam has already implemented the PK process for a variety of medicines. We are now further developing our laboratory capabilities to expand our database.
Dr. Razan Sakran, a senior clinical pharmacist in The Joan & Sanford Weil Division of Pediatric Hematology-Oncology at the Ruth Rappaport Children’s Hospital at Rambam, cites this example, “I have a two-year-old patient who is underweight and continues to lose weight. In this case, current dosing practices are inappropriate, so, together with Rambam’s specialist pediatric oncological physicians and the experts at Rambam’s Clinical Pharmacology Institute, we regularly evaluate the toddler’s treatment. We calculate and examine every angle before making a decision.”
Dr. Shifra Ash, director of the Pediatric Hematology & Oncology Division at Rambam, attests to the advantages of the PK method now being implemented at Rambam: “We hold long and comprehensive case-discussions; the patient’s medical history versus medical literature is addressed, we cross-reference calculations and tests, and consider the aggressiveness of the disease or treatment needed. We consider all this information when working on the optimal dosage of different medications and drug therapies. It is an important tool for addressing the medical challenges we face.”
Pharmacokinetics is still in its infancy, but during the recent International Meeting on Pediatric Hemato-Oncology held at Rambam’s Ruth Rappaport Children’s Hospital, in-depth professional discussions on this topic took place. Israeli and European experts reviewed therapeutic issues, innovations, and trends.
During the conference, a lecture was given on the topic, “Precision Dosing in Pediatric Oncology – Lots of Tradition, Little Evidence.” Presented by Professor Kurnick and, Dr. Sakran, focused on toddlers and infants under two. “In this age group, other processes happen,” says Dr. Sakran, “beyond body-weight and body-size data, we need to take the maturation processes of the body systems into account and the elimination of the drugs. Also the kidneys and liver work at a different rate than in older children and certainly in adults.”
When administering oncology drug therapies to such young children, the best way to determine dosage is by using mathematical models and considering all aspects of the disease. In these patients, one such method called allometric scaling finds the optimal dose an infant more accurately than conventional methods.
Professor Kurnick and Dr. Sakran agree, “Investments in skilled manpower, developing laboratory capabilities, and other resources are needed to expand the field and to make it an integral part of international treatment protocols.”