title: Population Pharmacokinetics of an Intranasally Administered Combination of Oxymetazoline and Tetracaine in Healthy Volunteers.
abstract: The primary objective of the current investigation was to establish the pharmacokinetic characteristics of oxymetazoline and tetracaine's primary metabolite, para-butylaminobenzoic acid (PBBA), after the intranasal administration of oxymetazoline/tetracaine. Thirty-six subjects contributing a total of 1791 plasma concentration results from 2 open-label trials were utilized. Model development was achieved using data from the second trial (N = 24) in which 0.3 mg oxymetazoline/18 mg tetracaine was administered. External model validation utilized data from the first trial (N = 12), which included doses of 0.3 mg oxymetazoline/18 mg tetracaine and 0.6 mg oxymetazoline/36 mg tetracaine. Oxymetazoline and PBBA dispositions were described by a 2-compartment model with first-order absorption. An allometric model for body weight was included on volumes and clearances to describe unexplained between-subject variability. The final oxymetazoline parameter estimates were ka4.41 h-1; peripheral volume 418 L; clearance 66.4 L/h; central volume 6.97 L; and intercompartmental clearance 419 L/h for a 70-kg subject. The final PBBA parameter estimates were ka8.51 h-1; peripheral volume 32.0 L; clearance 16.7 L/h; central volume 29.8 L; and intercompartmental clearance 2.43 L/h for a 70-kg subject. Between-subject variability ranged from 14% to 39% for oxymetazoline and from 10% to 94% for PBBA.
authors.affiliation: ContractKinetica, Columbia, MO, USA.|Center for Translational Medicine, School of Pharmacy, University of Maryland, Baltimore, MD, USA.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Cacek
authors.affiliation: Center for Translational Medicine, School of Pharmacy, University of Maryland, Baltimore, MD, USA.
authors.forename: Jogarao V S
authors.initials: JV
authors.lastname: Gobburu
authors.affiliation: Center for Translational Medicine, School of Pharmacy, University of Maryland, Baltimore, MD, USA.
authors.forename: Mathangi
authors.initials: M
authors.lastname: Gopalakrishnan
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000465:Algorithms; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001711:Biotransformation; D004338:Drug Combinations; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D014663:Nasal Decongestants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D059085:Nasal Sprays; D010109:Oxymetazoline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011153:Population; D013748:Tetracaine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult; D062366:para-Aminobenzoates / Q000097:blood
chemical_list: D000779:Anesthetics, Local; D004338:Drug Combinations; D014663:Nasal Decongestants; D059085:Nasal Sprays; D062366:para-Aminobenzoates; D013748:Tetracaine; C030553:4-n-butylaminobenzoic acid; D010109:Oxymetazoline
keywords: analgesiology/pain management; oxymetazoline; pharmacokinetics and drug metabolism; population pharmacokinetics; tetracaine