Re-examining Naloxone Pharmacokinetics After Intranasal and Intramuscular Administration Using the Finite Absorption Time Concept.

Background and objectives: Naloxone for opioid overdose treatment can be administered by intravenous injection, intramuscular injection, or intranasal administration. Published data indicate differences in naloxone pharmacokinetics depending on the route of administration. The aim of this study was to analyze pharmacokinetic data in the same way that we recently successfully applied the concept of the finite absorption time in orally administered drug formulations.

Methods: Using the model equations already derived, we performed least squares analysis on 24 sets of naloxone concentration in the blood as a function of time.

Results: We found that intramuscular and intranasal administration can be described more accurately when considering zero-order absorption kinetics for finite time compared with classical first order absorption kinetics for infinite time.

Conclusions: One-compartment models work well for most cases. Two-compartment models provide better details, but have higher parameter uncertainties. The absorption duration can be determined directly from the model parameters and thus allow an easy comparison between the ways of administration. Furthermore, the precise site of injection for intramuscular delivery appears to make a difference in terms of the duration of the drug absorption.