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Fattinger K, Benowitz NL, Jones RT, Verotta D. 
“Nasal mucosal versus gastrointestinal absorption of nasally administered cocaine”. 
Eur J Clin Pharmacol. 2000 Jul 08;56(4):305-10.
OBJECTIVE: Several xenobiotics, including cocaine, are dosed by the nasal route for systemic effects. The aim of this study was to estimate and compare cocaine input into the systemic circulation after oral and nasal dosing, and to determine the relevance of local absorption through the nasal mucosa.

METHODS: Cocaine was administered to healthy volunteers through the intravenous, oral, and nasal routes. Cocaine serum concentrations were measured at frequent intervals. From these data, the gastrointestinal, nasal, and nasal mucosa input rate functions were determined using nonparametric, subject-specific population deconvolution.

RESULTS: After oral dosing, cocaine input into systemic circulation increased slowly and peaked around 45 min after ingestion. The median systemic bioavailability after oral dosing was 33. After nasal dosing, drug input was substantial even during the first minute and showed two peaks at 10 min and 45 min after ingestion. Since the second peak after nasal dosing closely resembled drug input after oral administration, we hypothesized that, after nasal administration, a part of the dose is swallowed and thereafter absorbed gastrointestinally. The data from the sessions with nasal cocaine administration were reanalyzed assuming the same shape for gastrointestinal drug input as after oral dosing. The fraction absorbed through the nasal mucosa was estimated to be 19 (95 CI: 11-26). The fraction absorbed through the nasal mucosa contributed 31 (95 CI: 23-37) of total systemic cocaine exposure.

CONCLUSIONS: Our data suggest that the main reason addicts prefer nasal to oral cocaine dosing is faster absorption, enhancing the subjective effects rather than higher bioavailability.
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