Pharmacokinetics and relative bioavailability of fentanyl pectin nasal spray

100 - 800 g in healthy volunteers.

Fentanyl is an opioid analgesic very studied with lipophilic properties suitable for
nasal administration. Studies of other conventional solutions of non-gelling fentanyl
nasally administered have demonstrated shorter intervals to reach maximum
plasma concentrations with higher bioavailability, compared with the oral and
transmucosal way. These features indicate that the pathway fentanyl nasal
provides clinical benefits, particularly in the treatment of breakthrough cancer pain,
in which a rapid onset of action is preferable. A previous study of efficacy of a
nasal solution in patients shown to provide relief of breakthrough pain in 5 minutes
from the nasal administration.
Fentanyl pectin nasal spray (FPNS) is formulated as a solution utilizing
PecSys;pectin based enabling technology (Archimedes). On contact with the
nasal mucosa the formulation will gel and modulate fentanyl absorption while
limiting nasal drip or runoff. This single-dose volunteer study compared the
pharmacokinetics of FPNS 100, 200, 400, and 800 g doses and assessed
bioavailability relative to oral transmucosal fentanyl (OTFC) 200 g. Safety and
dose proportionality were also examined. SUBJECTS AND METHODS: 16, opioid-
nave subjects were dosed on five separate visits under naltrexone block. FPNS
doses were administered using a Pfeiffer device delivering 100 l. Devices were
filled with either 1.57 mg/ml (100 and 200 g dosing) or 6.28 mg/ml
fentanyl citrate (400 and 800 g). Venous blood samples were collected up to 48 h
after dosing and plasma fentanyl concentrations measured.
Median tmax values for FPNS ranged from 15 to 21 min post-dose and were dose-
independent. At 200 g Cmax values were 2.3-fold higher for FPNS compared with
OTFC. Mean relative bioavailability of FPNS to OTFC ranged from 103% to 163%.
Dose proportionality for Cmax and AUC0-1 across the FPNS range was
statistically confirmed. Drug absorption also increased in a close to dose-
proportional manner for AUC0-inf.
FPNS has a shorter tmax, higher Cmax and greater bioavailability than OTFC and
is well tolerated. The dose proportionality of Cmax and AUC0-1 was demonstrated.
It is concluded that the pharmacokinetic profile of FPNS suggests this product is
suitable for clinical investigation in breakthrough pain in cancer patients.
Reference:
1. Fisher, A., Watling, M., Smith, A., Knight, A. (2010). Farmacocintica y
biodisponibilidad relativa del espray intranasal de fentanilo en pectina
100 - 800 g en voluntarios sanos. International Journal of clinical
pharmacology and therapeutics. Vol. 48. 12 pp. 860- 867.