Naloxone
Naloxone. Pure µ-opioid receptor antagonist — competitive blockade with no agonist activity. Reverses opioid overdose in seconds (IV) to… Intranasal half-life 1.1 h.
Pure µ-opioid receptor antagonist — competitive blockade with no agonist activity. Reverses opioid overdose in seconds (IV) to minutes (IN). OTC nasal spray (Narcan) available in most US states without prescription; precipitates opioid withdrawal in opioid-dependent users.
PK: the record carried TWO DIFFERENT VOLUMES for one drug, which a disposition volume cannot have. The intravenous 56 L is verbatim but is the CENTRAL COMPARTMENT of a biexponential fit, not a whole-body volume; the intranasal 200 L appears nowhere in its cited paper at all. Both are replaced by one route-independent 37.96 L, the sum of three compartment volumes in Dowling 2008 (PMID:18641540), which dosed intravenously, intramuscularly and intranasally. That paper also supplies the FIRST LITERAL, NAMED, NUMERIC absorption rate constant found anywhere in this audit series — "Ka (intramuscular), 0.65; and Ka (intranasal), 1.52" — and the intranasal figure is stored. FORMULATION CAVEAT: Dowling sprayed the dilute injectable solution and measured only 4% bioavailability, so its RATE is taken but not its extent; the 47% retained here is from a purpose-built concentrated spray. The half-life is re-cited: the old abstract MISLABELS ITS OWN UNITS, printing rate constants in reciprocal minutes as half-lives. THE SAFETY FACT IS IN THE RECORD OWN CITATION: naloxone is shorter-acting than the opioids it reverses, so "repeated naloxone dosing often is required to prevent the recurrence of respiratory depression", and duration of reversal is set by the opioid dissociation, not by this curve.
Pharmacokinetics
- IV — t½ 1.1 h · F 100% · Vd 37.96 L
- Intranasal — t½ 1.1 h · F 47% · ka 1.52 h⁻¹ · Vd 37.96 L
Sources: PMID:31556537, PMID:3963538, PMID:9686407, PMID:18641540, PMID:1267205, PMID:6519154