Abstract
Background and objective
Narcotic analgesics such as hydromorphone undergo an extensive first-pass effect resulting in a low systemic bioavailability following oral administration. Alternative dosing routes, such as rectal and intranasal (IN) routes, have been suggested as options for oral or intravenous administration. Rhinitis and pharmacological agents used for treatment are considered factors that could alter the rate and extent of absorption of drugs administered by the nasal route. The purpose of this study was to evaluate the pharmacokinetics of intranasal hydromorphone hydrochloride (HCl) in patients with vasomotor rhinitis.
Methods
Ten patients completed the randomised, three-way crossover study. During the three treatment periods, a single dose of hydromorphone HCl 2.0mg was administered via intravenous infusion (treatment A) and the intranasal route without (treatment B) or with (treatment C) vasoconstrictor pretreatment for rhinitis. Blood samples were collected serially from 0 to 16 hours. Noncompartmental methods were used to determine pharmacokinetic parameters.
Results
Maximum plasma concentrations were 3.69 and 3.38 μg/L for treatments B and C, respectively. Mean (% coefficient of variation) bioavailability of intranasal hydromorphone was 54.4% (34.8) and 59.8% (22.1) with and without pretreatment, respectively. Pretreatment of rhinitis did not significantly affect the rate or extent of absorption of hydromorphone in this study. There was not a significant difference in bioavailability between treated and untreated rhinitis.
Conclusions
This study found intranasal administration of hydromorphone in patients experiencing vasomotor rhinitis had acceptable bioavailability and a pharmacokinetic profile comparable to previous studies. These data support further investigation of this single-dose delivery system for clinical use.
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Notes
The use of trade names is for product identification purposes only and does not imply endorsement.
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Acknowledgements
This study was financially supported by Intranasal Technology, Inc., Lexington, KY, USA. Dr Rudy is currently employed by Intranasal Technology, Inc. Drs Wermeling and Archer are paid consultants to Intranasal Technology, Inc.
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Davis, G.A., Rudy, A.C., Archer, S.M. et al. Bioavailability and Pharmacokinetics of Intranasal Hydromorphone in Patients Experiencing Vasomotor Rhinitis. Clin. Drug Investig. 24, 633–639 (2004). https://doi.org/10.2165/00044011-200424110-00002
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DOI: https://doi.org/10.2165/00044011-200424110-00002