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Population Pharmacokinetics of an Intranasally Administered Combination of Oxymetazoline and Tetracaine in Healthy Volunteers
Author(s) -
Cacek Anthony T.,
Gobburu Jogarao V. S.,
Gopalakrishnan Mathangi
Publication year - 2017
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.799
Subject(s) - oxymetazoline , tetracaine , volume of distribution , pharmacokinetics , chemistry , anesthesia , pharmacology , medicine , agonist , biochemistry , receptor , lidocaine
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 k a 4.41 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 k a 8.51 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.