Dustri Online Services

Search Results

Books: 0	Journals: 1	Articles: 2

Original Research

Pharmacokinetic comparisons of three nasal fentanyl formulations; pectin, chitosan and chitosan-poloxamer 188

A. Fisher, M. Watling, A. Smith and A. Knight

Price
42.00 $

Add to Cart

Price

42.00 $

Volume 48 p. 138 - 145

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 48 – No. 2/2010 (138-145)

Pharmacokinetic comparisons of three nasal fentanyl formulations; pectin, chitosan and chitosan-poloxamer 188

A. Fisher¹, M. Watling¹, A. Smith¹ and A. Knight²

¹Archimedes Development Limited, Albert Einstein Centre, Nottingham Science and Technology Park, University Boulevard, Nottingham, and ²Evicom Limited, Somerset House, Teddington, UK
Objectives: To optimize the absorption profile and reduce C_max, three new fentanyl nasal spray formulations have been developed: fentanyl pectin (FPNS), fentanyl chitosan (FChNS) and fentanyl in chitosan-poloxamer 188 (FChPNS). The venous pharmacokinetic profiles and tolerability of these formulations were assessed and compared with oral transmucosal fentanyl citrate (OTFC) lozenge. Subjects and methods: This randomized, open-label, crossover study was conducted in opioid-naïve, healthy adult volunteers. Subjects were dosed under naltrexone blockade on four occasions with three nasal sprays (100 µg in 100 µl) and OTFC 200 µg. Fentanyl venous plasma concentrations were measured up to 24 h post-dose. Tolerability was assessed by clinical nasal assessments and a nasal reactogenicity questionnaire. Results: 18 subjects were enrolled and completed the study. The mean dose-normalized AUC_0-∞ for each nasal formulation was significantly higher (p < 0.05) compared with OTFC. Bioavailability compared with OTFC was significantly greater for all nasal fentanyl formulations (FPNS 132.4%, FChNS 154.1%, FChPNS 122.3%). Median t_max (FPNS 0.33 h, FChNS 0.17 h, FChPNS 0.26 h) were significantly (p < 0.001) reduced (OTFC 1.5 h) and mean C_max significantly increased with all nasal formulations compared with OTFC. Nasal reactogenicity symptom incidence was lowest for the FPNS formulation (FPNS 2, FChNS 28 and FChPNS 45). Conclusions: All nasal formulations demonstrated significantly increased systemic exposure and reduced times to peak plasma values compared with OTFC. The FPNS formulation exhibited the most favorable nasal and general tolerability profiles. It appears suitable for further investigation in breakthrough cancer pain management.Correspondence to:
A. Fisher, PhD
Archimedes Development Limited
Albert Einstein Center
Nottingham Science and Technology Park
University Boulevard
Nottingham, NG7 2TN, UK
Email: [email protected]

Bioavailability Section

Pharmacokinetics and relative bioavailability of fentanyl pectin nasal spray 100 – 800 µg in healthy volunteers

A. Fisher, M. Watling, A. Smith and A. Knight

Price
42.00 $

Add to Cart

Price

42.00 $

Volume 48 p. 860 - 867

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 48 – No. 12/2010 (860-867)

Pharmacokinetics and relative bioavailability of fentanyl pectin nasal spray 100 – 800 µg in healthy volunteers

A. Fisher¹, M. Watling¹, A. Smith¹ and A. Knight²

¹Archimedes Development Limited, Albert Einstein Centre, Nottingham Science and Technology Park, University Boulevard, Nottingham, and ²Evicom Limited, Somerset House, Teddington, UK
Objectives: 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 µg doses and assessed bioavailability relative to oral transmucosal fentanyl (OTFC) 200 µg. Safety and dose proportionality were also examined. Subjects and methods: 16, opioid-naïve subjects were dosed on five separate visits under naltrexone block. FPNS doses were administered using a Pfeiffer device delivering 100 µl. Devices were filled with either 1.57 mg/ml (100 and 200 µg dosing) or 6.28 mg/ml fentanyl citrate (400 and 800 µg). Venous blood samples were collected up to 48 h after dosing and plasma fentanyl concentrations measured. Results: Median t_max values for FPNS ranged from 15 to 21 min post-dose and were dose-independent. At 200 µg C_max 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 C_max and AUC_0–1 across the FPNS range was statistically confirmed. Drug absorption also increased in a close to dose-proportional manner for AUC_0–inf. Conclusions: FPNS has a shorter t_max, higher C_max and greater bioavailability than OTFC and is well tolerated. The dose proportionality of Cmax and AUC_0–1 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.Correspondence to:
A. Fisher, PhD
Archimedes Development Limited
Albert Einstein Centre
Nottingham Science and Technology Park
University Boulevard, Nottingham, NG7 2TN, UK
Email: [email protected]

Shopping Overview

Shopping Overview
Type	Qtty	Discount	VAT	Price
Your basket is empty

View Cart

Search Results

Shopping Overview

Send us an E-Mail