A multiple-dose Phase I study of intranasal hydromorphone hydrochloride in healthy volunteers

Anita C. Rudy, Barbara A. Coda, Sanford M. Archer, Daniel P. Wermeling

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish
Pages (from-to)1379-1386
Number of pages8
JournalAnesthesia and Analgesia
Volume99
Issue number5
DOIs
StatePublished - Nov 2004

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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