Pharmacokinetics and dose proportionality of fentanyl sublingual spray: a single-dose 5-way crossover study.

Background: Fentanyl sublingual spray is a novel formulation of fentanyl for sublingual delivery that was designed to enhance the rate and extent of absorption of fentanyl for management of breakthrough cancer pain (BTCP).

Objectives: The primary objective of this study was to determine the pharmacokinetics and dose proportionality of 5 different doses (100, 200, 400, 600, and 800 μg) of fentanyl sublingual spray in healthy subjects under fasted conditions (part A); the secondary objective was to assess the effects of temperature and pH in the oral cavity on relative bioavailability of fentanyl (part B).

Methods: Analyses were performed on venous blood samples drawn 5 min to 36 h after administration of fentanyl sublingual spray (Subsys(®), Insys Therapeutics, Inc.

Single-dose pharmacokinetics of fentanyl sublingual spray and oral transmucosal fentanyl citrate in healthy volunteers: a randomized crossover study.

Background: Fentanyl sublingual spray (FSS) is a novel fentanyl formulation recently developed for the treatment of breakthrough cancer pain, which is characterized by a fast onset and a relatively short duration.

Objective: To compare rate of absorption and systemic bioavailability between FSS and oral transmucosal fentanyl citrate (OTFC) in healthy volunteers.

Methods: This randomized 3-way crossover study involved 29 healthy volunteers (25 men and 4 women; mean age, 35 years) who received single doses of FSS (400 μg), OTFC (400 μg), and intravenous fentanyl citrate (100 μg) separated by washout periods of ≥7 days.

Novel site-specific chemical delivery system as a potential mydriatic agent: formation of phenylephrine in the iris-ciliary body from phenylephrone chemical delivery systems.

The objective of this study was to test the three novel ester derivatives of phenylephrone (isovaleryl, phenylacetyl, and pivalyl esters) as potential site-specific chemical delivery systems. The mydriatic effect and ocular distribution/metabolism of these compounds were studied by topical application to the eyes of normal rabbits. It was assumed that a reduction-hydrolysis sequence could produce the active phenylephrine in the iris-ciliary body tissues.

Permeability of chemical delivery systems across rabbit corneal (SIRC) cell line and isolated corneas: a comparative study.

The purpose of this study was to investigate the corneal permeability of phenylephrone chemical delivery systems (CDS) across isolated cornea and to evaluate the utility of the SIRC cell line (epithelial cells originating from rabbit cornea) as an in vitro model for predicting the ocular permeability. The effect of benzalkonium chloride (BAC) on the drug permeability through SIRC cell layers was also studied. The transport of phenylephrone CDS across the isolated cornea of the albino rabbit was measured at various pH values using a two-chamber glass diffusion cell, and the results were compared with the reported permeability values across SIRC cells of rabbit origin.

Chemical delivery systems: evaluation of physicochemical properties and enzymatic stability of phenylephrone derivatives.

The physicochemical properties and enzymatic stability of esters of phenylephrone, synthesized on the basis of the chemical delivery system (CDS) concept, were studied as a new class of mydriatic agents. Potentiometrically determined ionization constants (pKa) of the novel compounds were in the range 7.19-7.