Fentanyl Metabolism in Obese Adolescents

Obesity represents one of the most important public health issues according to the World Health Organization. It has reached epidemic proportions globally, with approximately 1.5 billion overweight adults 20 years and older and at least 600 million of them clinically obese in 2008. According to the most recent NHANES survey (2003-2006), over two-third of the adults in the US are overweight or obese (overweight 68%, half of them obese) and about 17.6% of children and adolescents aged 12 to 19 were considered overweight or obese.

Obesity has also become an important challenge for the anesthesiologist. Safety and drug dosing particularly within the field of pediatric anesthesia, is of paramount concern as it can affect patient outcomes. Data collected in the United Kingdom from more than 100,000 anesthetized pediatric patients showed that a critical incident is twice as likely to occur in an obese child in the preoperative period as in an obese adult. A possible explanation may be linked to the lack of precision in drug dosing for these obese patients.

Fentanyl is a frequently used opioid analgesic in pediatric and adult anesthesia. Fentanyl is commonly administered to pediatric patients undergoing anesthesia as it is has a high potency, a rapid onset and a short duration of action. Due to these properties intravenously administered fentanyl is well suited as an analgesic compound in general anesthesia in pediatric patients.

The pharmacokinetics of fentanyl in adults have been well documented. Although there are some studies investigating the pharmacokinetic properties of oral, transmucosal and intravenous fentanyl preparations in children, the disposition of fentanyl in pediatric patients has not been sufficiently described. Several studies in infants and children report age-dependent differences in the pharmacokinetic/ pharmacodynamic parameters of intravenously administered fentanyl.

Currently there are no data available about the pharmacokinetics/ pharmacodynamics of fentanyl in adolescent obese patients.

Inclusion criteria

• 1. The subject will be an inpatient or outpatient admitted for at least 24 hours observation as part of the surgical plan of care

• The BMI will be calculated using height and weight and will include the 5th to 84th percentile for the control group and greater than or equal to 95th percentile for the obese adolescents.

• All racial and ethnic groups will be included.

Exclusion criteria

• Any patient that is pregnant or lactating.
• Prior exposure to any opioid including fentanyl within a 24 hour period.
• Patients with known hypersensitivity to any opioids.
• History of central nervous system dysfunction and active upper airway disease and liver and renal disease. Patients diagnosed with renal or liver disease as evidenced by abnormal function tests within the past 12 months will be excluded.
• Patients who are treated with drugs known to affect the cytochrome P450 3A (CYP3A4), like antiepileptics, imidazole derivates, macrolides, corticosteroids and grapefruit juice

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