title: A multiple-dose phase I study of intranasal hydromorphone hydrochloride in healthy volunteers.
abstract: We evaluated the pharmacokinetics, tolerability, and safety of 1 and 2 mg of intranasal hydromorphone hydrochloride in an open-label, single- and multiple-dose study. This Phase I study was conducted in 24 healthy volunteers (13 men and 11 women). Intranasal doses were delivered as 0.1-mL metered-dose sprays into one or both nostrils for 1- and 2-mg doses, respectively. Venous blood samples were taken serially from 0 to 12 h after the first single dose and the last (seventh) multiple dose. Plasma hydromorphone concentrations were determined by liquid chromatography/mass spectrometry/mass spectrometry. Noncompartmental analysis was used to estimate pharmacokinetic variables. After 7 intranasal doses of 1 and 2 mg (once every 6 h), mean +/- sd peak plasma concentrations of 2.8 +/- 0.7 ng/mL and 5.3 +/- 2.3 ng/mL, respectively, were observed. The median time to peak concentration was 20 min for both single and multiple doses. Dose proportionality was observed for the 1- and 2-mg doses. Adverse events included somnolence, dizziness, and bad taste after dose administration. Intranasal hydromorphone hydrochloride was well tolerated and demonstrated rapid nasal drug absorption and predictable accumulation. These results support clinical investigation of hydromorphone hydrochloride nasal spray for use as an alternative to oral and IM administration.
authors.affiliation: *Intranasal Technology, Inc., Lexington, Kentucky; †Department of Anesthesiology, University of Washington, Seattle, Washington; ‡McKenzie Anesthesia Group, Springfield, Oregon; §Division of Otolaryngology-Head & Neck Surgery, ∥ University of Kentucky A. B. Chandler Medical Center, Lexington, Kentucky; and University of Kentucky College of Pharmacy, Lexington, Kentucky.
authors.forename: Anita C
authors.initials: AC
authors.lastname: Rudy
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Coda
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Archer
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Wermeling
mesh_terms: D000042:Absorption; D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry; D036501:Metered Dose Inhalers
chemical_list: D000701:Analgesics, Opioid; D004091:Hydromorphone