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Fentanyl buccal tablet for the treatment of breakthrough pain: pharmacokinetics of buccal mucosa delivery and clinical efficacy.

Darwish M, Hamed E, Messina J - Perspect Medicin Chem (2010)

Bottom Line: Fentanyl buccal tablet (FBT; FENTORA((R)), Cephalon, Inc.) employs OraVescent((R)) drug delivery technology, which enhances the rate and extent of fentanyl absorption.OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism.The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP.

View Article: PubMed Central - PubMed

Affiliation: Cephalon, Inc., Frazer, PA 19355, USA.

ABSTRACT
The treatment of breakthrough pain (BTP), a transitory exacerbation of pain that occurs on a background of otherwise-controlled, persistent pain, requires an opioid formulation and/or method of administration that can provide rapid and extensive systemic exposure. Fentanyl buccal tablet (FBT; FENTORA((R)), Cephalon, Inc.) employs OraVescent((R)) drug delivery technology, which enhances the rate and extent of fentanyl absorption. OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism. The resulting pharmacokinetic profile of FBT is characterized by greater bioavailability and a higher early systemic exposure compared with the earlier oral transmucosal fentanyl citrate formulation. In clinical studies of opioid-tolerant patients with cancer-related and noncancer-related BTP, FBT has provided consistent and clinically relevant improvements in pain intensity and pain relief relative to placebo, with a safety and tolerability profile that is generally typical of that observed with other potent opioids. The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP.

No MeSH data available.


Related in: MedlinePlus

Changes in pH over the surface of the dissolving fentanyl buccal tablet during the initial 5-minute time interval. Adapted with permission from Durfee et al.15
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Related In: Results  -  Collection


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f1-pmc-2010-011: Changes in pH over the surface of the dissolving fentanyl buccal tablet during the initial 5-minute time interval. Adapted with permission from Durfee et al.15

Mentions: A hypothesis explaining how the different reactions involved in the dissolution of tablets via the OraVescent system induce pH changes has been published elsewhere; the reactions are shown in Figure 115 and Table 1.18 In brief, as the tablet begins to dissolve, the local environment becomes more acidic because of the dissolved citric acid and CO2. In this acidic environment, the available fentanyl becomes almost completely ionized and, therefore, its aqueous solubility is high. As the reactions progress, CO2 is released and the pH increases in the presence of a larger number of basic cations, rendering the dissolved fentanyl nonionized. Concurrently, the accompanying CO2 liberation is thought to improve membrane permeation of fentanyl. As the pH increases, a physiological “pump,” caused by the local concentration gradient of nonionized fentanyl, is created, which pushes the drug into and across the lipid barrier of the buccal mucosa.15,18


Fentanyl buccal tablet for the treatment of breakthrough pain: pharmacokinetics of buccal mucosa delivery and clinical efficacy.

Darwish M, Hamed E, Messina J - Perspect Medicin Chem (2010)

Changes in pH over the surface of the dissolving fentanyl buccal tablet during the initial 5-minute time interval. Adapted with permission from Durfee et al.15
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2901636&req=5

f1-pmc-2010-011: Changes in pH over the surface of the dissolving fentanyl buccal tablet during the initial 5-minute time interval. Adapted with permission from Durfee et al.15
Mentions: A hypothesis explaining how the different reactions involved in the dissolution of tablets via the OraVescent system induce pH changes has been published elsewhere; the reactions are shown in Figure 115 and Table 1.18 In brief, as the tablet begins to dissolve, the local environment becomes more acidic because of the dissolved citric acid and CO2. In this acidic environment, the available fentanyl becomes almost completely ionized and, therefore, its aqueous solubility is high. As the reactions progress, CO2 is released and the pH increases in the presence of a larger number of basic cations, rendering the dissolved fentanyl nonionized. Concurrently, the accompanying CO2 liberation is thought to improve membrane permeation of fentanyl. As the pH increases, a physiological “pump,” caused by the local concentration gradient of nonionized fentanyl, is created, which pushes the drug into and across the lipid barrier of the buccal mucosa.15,18

Bottom Line: Fentanyl buccal tablet (FBT; FENTORA((R)), Cephalon, Inc.) employs OraVescent((R)) drug delivery technology, which enhances the rate and extent of fentanyl absorption.OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism.The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP.

View Article: PubMed Central - PubMed

Affiliation: Cephalon, Inc., Frazer, PA 19355, USA.

ABSTRACT
The treatment of breakthrough pain (BTP), a transitory exacerbation of pain that occurs on a background of otherwise-controlled, persistent pain, requires an opioid formulation and/or method of administration that can provide rapid and extensive systemic exposure. Fentanyl buccal tablet (FBT; FENTORA((R)), Cephalon, Inc.) employs OraVescent((R)) drug delivery technology, which enhances the rate and extent of fentanyl absorption. OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism. The resulting pharmacokinetic profile of FBT is characterized by greater bioavailability and a higher early systemic exposure compared with the earlier oral transmucosal fentanyl citrate formulation. In clinical studies of opioid-tolerant patients with cancer-related and noncancer-related BTP, FBT has provided consistent and clinically relevant improvements in pain intensity and pain relief relative to placebo, with a safety and tolerability profile that is generally typical of that observed with other potent opioids. The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP.

No MeSH data available.


Related in: MedlinePlus