Christina Gade 1, Hanne Rolighed Christensen 1, Kim Peder Dalhoff 1, Jens Christian Holm 2, Helle Holst 1
Department of Clinical Pharmacology, Copenhagen University Hospital, Bispebjerg and Frederiksberg. Denmark
Children’s Obesity Clinic, European Center of Management (EASO). Department of Pediatrics, Zealand University Hospital, Holbaek. Denmark
What is known about this subject?
- Physiological changes accompanying obesity may result in altered drug pharmacokinetics
- Dosing children with obesity by the use of traditional pediatric dosage strategies may result in sub- or supra-therapeutic doses
- Several reviews have described metrics of body size to adjust dose in children with obesity i.e. IBW, ABW and allometric scaling
What This Study Adds:
- This study highlights the shortage of dosing guidelines in children with obesity.
- A large inter-individual variability in dosing regimens was found, and metrics of body size were not applied in the clinic
- PK/PD studies are needed. Meanwhile, dosing guidelines should be standardized by pediatricians in collaboration with clinical pharmacologists
Obesity can affect the pharmacokinetics of most drugs, which may result in under- or overdosing if traditional pediatric dosing strategies are used.
To investigate currently applied dosing strategies in children with Overweight/Obesity, in a clinical treatment facility. In particular, whether dosing guidelines were available and metrics of body size applied.
A retrospective cohort study of 200 patients admitted to the Danish Children´s Obesity Clinic. Data were collected from 2008 to 2015. Overweight /obese children ≤ 18 years were included if they had at least one drug prescriptions.
Overall there were 658 prescriptions, primarily analgesics, psychotropics, asthma medications, and antibiotics. Except for one prescription, guidelines for dosage of overweight/obese children were not available in the clinic. In one prescription of gentamicin, the dose was adjusted by a metric body size. Otherwise dose was predominately prescribed either by total body weight or as fixed dose by age, in accordance with the recommendations of normal weight children. In drugs with a narrow therapeutic interval, we found large inter-individual variations in dosing regimens i.e. for gentamicin, paracetamol and prednisolone. Reduction of dose to the maximum recommended adult dose was common practice, when the dose calculated by total body weight (i.e. mg/kg) exceeded this maximum.
This study highlights the shortage of dosing guidelines in OW/OB children. We found a large inter-individual variability in dosing regimens, even in drugs with narrow therapeutic intervals. The clinicians are left with “best practice”, as evidence-based dosimng regimens are missing for many drugs prescribed during childhood.