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 k 4.41 h ; 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 8.51 h ; 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.

Hemodynamic and pharmacokinetic analysis of oxymetazoline use during nasal surgery in children

“…We postulate that the absorption from the nasal mucosa may be slowed by the drug's local vasoconstrictor effect on the vasculature of the nasal mucosa. This may reduce systemic absorption and contribute to hemodynamic stability and observed serum concentrations similar to those reported in other studies, despite larger and repeated oxymetazoline dosing and a higher bioavailability with the current pledget administration …”

“…This may reduce systemic absorption and contribute to hemodynamic stability and observed serum concentrations similar to those reported in other studies, despite larger and repeated oxymetazoline dosing and a higher bioavailability with the current pledget administration. 8,13 Although oxymetazoline is readily available as an over-the-counter medication, its hemodynamic profile may be concerning especially when higher than recommended doses are administered. The impetus for this study was the concern of the safety of the drug, given anecdotal reports of cardiovascular collapse.…”

“…The model was parameterized in terms of clearance (CL), intercompartmental clearance (Q), two volumes of distribution (V1, V2) and an absorption half‐life (Tabs 1/2 ). Data were limited, so to estimate the relative bioavailability of the nasal pledgets (F PLEG/SPRAY ) compared to spray, we used prior information from a study of oxymetazoline nasal spray in adults . Adding the prior information to the compartment models enabled us to estimate this relative bioavailability and absorption half‐times.…”

“…Data were limited, so to estimate the relative bioavailability of the nasal pledgets (F PLEG/SPRAY ) compared to spray, we used prior information from a study of oxymetazoline nasal spray in adults. 13 Adding the prior information to the compartment models enabled us to estimate this relative bioavailability and absorption half-times. The parameter estimates were standardized for a body weight of 70 kg using an allometric modelP: 14,15 Pi…”

Anestesia dental local sin aguja: Una revisión integrativa de la literatura.

“…Kovanaze se emplea en el dispositivo descartable BD Acusspray [32][33][34][35]37,38 , el cual crea una pulverización al forzar el líquido a través de un atomizador de remolino de presión cuando se acciona la barra que contiene al émbolo 39 (Fig.5). Cada pulverización de 0.2 mL contiene 6 mg de clorhidrato de tetracaína y 0.1mg de clorhidrato de oximetazolina, equivalente a 5.27 mg de tetracaína y 0.08mg de oximetazolina.…”