Abstract 460 Poster Session III, Monday, 5/3 (poster 205)

Background: Naloxone is an opiate antagonist that is structurally similar to morphine. Naloxone is used diagnostically in the pediatric patient who presents with altered mental status/respiratory depression, to reverse conscious sedation, and in suspected clonidine and valproic acid overdoses. Like morphine, naloxone is metabolized in the liver primarily by conjugation to glucuronide, and then eliminated in the urine. Despite anecdotal reports of parenteral naloxone administration producing a positive opiate urine drug screen, published data have failed to confirm this finding.

Objective: To determine whether naloxone produces a positive urine opiate screen in an in vitro analysis.

Methods: Subjects were 6 healthy, adult volunteers who had no significant past medical history, denied illicit drug use, and were not taking any medications. The setting was the clinical laboratory of an urban children's hospital. Incremental concentrations of naloxone (0, 100, 1000, 5000, 10,000, and 100,000 ng/ml) were added to each of the subjects' urine specimens; samples were then quantitatively analyzed by the cloned enzyme donor immunoassay (CEDIA) on the Hitachi 917 system. A positive urine opiate screen by this assay was set at concentration > 300 ng/ml. This assay has a 100% sensitivity for detection of morphine and 81% for detection of the morphine glucuronide metabolite.

Results: As the concentration of naloxone was consecutively increased from 0 to 100,000 ng/ml, mean urine enzyme activity for opiates was 172 ± 2, 177 ± 1, 204 ± 3, 278 ± 36, 365 ± 6, and 605 ± 10 enzyme units, respectively. At naloxone concentrations up to 5,000 ng/ml, all urine specimens were negative for opiate. At concentration 10,000 ng/ml and higher, all samples were positive for opiate. There was a significant correlation (r = 0.93, p < 0.001) between urinary enzyme activity for opiate and naloxone concentration in urine. Naloxone pharmacokinetics (25-40% urinary elimination of naloxone glucuronide within 6 hours) are such that administration of a therapeutic dose (2 mg) to a healthy 20 kg child could lead to a urinary concentration of at least 6,666 ng/ml, if one assumes a urine output of 1 cc/kg/hr. In the presence of dehydration or after repeat doses of naloxone, the urinary concentration of naloxone could exceed 13,000 ng/ml, which would produce a positive urinary opiate drug screen in this assay.

Conclusion: These data indicate that naloxone in vitro can produce a positive urine opiate drug screen; this finding supports clinical observations of this occurrence.