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Chronic non-cancer pain: Focus on once-daily tramadol formulations.

Coluzzi F, Mattia C - Ther Clin Risk Manag (2007)

Bottom Line: New once-daily (OD) formulations of tramadol have been marketed in various countries, in order to offer the advantage of a reduced dosing regimen and to improve patients' compliance.This review focuses on the technology, pharmacology, clinical efficacy, and safety of different once-daily tramadol formulations.Hydrophilic vs hydrophobic matrix systems and newer technologies used in once-daily formulations to control drug delivery are discussed.

View Article: PubMed Central - PubMed

Affiliation: ICOT - Polo Pontino, Rome, Italy; Department of Anesthesia, Intensive Care Medicine and Pain Therapy, University "La Sapienza" Rome, Italy.

ABSTRACT
Despite progress in pain management, chronic non-cancer pain (CNCP) represents still a clinical challenge. The efficacy and safety profile of tramadol make it suitable as a long-term treatment in a variety of CNCP conditions. New once-daily (OD) formulations of tramadol have been marketed in various countries, in order to offer the advantage of a reduced dosing regimen and to improve patients' compliance. This review focuses on the technology, pharmacology, clinical efficacy, and safety of different once-daily tramadol formulations. Hydrophilic vs hydrophobic matrix systems and newer technologies used in once-daily formulations to control drug delivery are discussed. Three randomized controlled trials (RCTs) established OD tramadol analgesic efficacy to be superior to that of placebo for pain management and functional improvement in patients with osteoarthritis. Three RCTs demonstrated similar rates of efficacy between OD tramadol and immediate-release (IR) or sustained-release (SR) formulations, with a better adverse events profile. An open trial on long term tolerability showed that OD tramadol is generally safe in rheumatological pain treatment.

No MeSH data available.


Related in: MedlinePlus

Mean plasma concentration-time profile for racemic tramadol (sum of both enantiomers) after a single oral dose in the fasting state of three different formulations: OD Tramadol Contramid® 200 mg (Labopharm), OD Tramadol 200 mg (Zambon), and OD Tramadol 200 mg (SMB Technology) (Malonne et al 2003; Hernandez-Lopez et al 2006).
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fig1: Mean plasma concentration-time profile for racemic tramadol (sum of both enantiomers) after a single oral dose in the fasting state of three different formulations: OD Tramadol Contramid® 200 mg (Labopharm), OD Tramadol 200 mg (Zambon), and OD Tramadol 200 mg (SMB Technology) (Malonne et al 2003; Hernandez-Lopez et al 2006).

Mentions: Only recently, a randomized controlled trial comparing two different OD tramadol formulations has been published by Hernandez-Lopez et al (2006). This is the first study that compares the bioavailability of a currently marketed OD tramadol formulation 200 mg using an hydrophobic matrix (Zambon, Spain) with the new OD tramadol formulation 200 mg using the Contramid® technology (Labopharm, Canada), both given as a single dose in the fasting state. 24 of 26 subjects were evaluable for the pharmacokinetic analysis of racemic tramadol and racemic O-demethyltramadol. All pharmacokinetic parameters (AUC, Cmax, C24h, and Tmax) were significantly higher for tramadol Contramid® (p < 0.0004), whereas the elimination half-life (T½) was significantly shorter (7.4 vs 14.9 h, p = 0.0001). Following tramadol Contramid® oral administration, mean plasma concentrations maintained a plateau above 200 ng/ml for a long duration (≥12h) from 4 h through 16 h after dose, while for the reference formulation the plasma levels were maintained for only 2 h, from 4 h through 6 h. Mean plasma concentration of tramadol at 24 h were significantly higher after tramadol Contramid® administration (38.9 vs 26.2 ng/ml p = 0.0001). As the confidence intervals fall outside of the range of acceptability for bioequivalence, these formulations cannot be considered bioequivalent. OD tramadol using Contramid® technology seems to have a better controlled-release profile and can be evaluated to be suprabioavailable. Finally, authors compared their results with those obtained by Malonne et al (2004) with the hydrophilic once-daily tramadol formulation 200 mg (SMB Technology, Belgium). When comparing the Tmax, expressed as median (min-max), the following values were observed: OD tramadol Contramid® (Labopharm) 9.0 h (2–16), OD tramadol (Zambon) 4.5 h (2–12), and OD tramadol (SMB Technology) 10 h (6–12) (Figure 1). The hydrophilic formulation (SMB Technology) showed a lag during which no appreciable drug absorption occurs, and the maximum concentration was achieved after about 10 hours, followed by a fast elimination process, similar to the immediate-release formulations. As shown in Figure 1, there was not a plateau in the plasma concentration-time curve. Thus the author concluded that this should be considered a “delayed-release” formulation, whereas the other two (using the hydrophobic matrix and the Contramid® technology, respectively from Zambon and Labopharm) showed pharmacokinetics characteristics of “controlled-release” formulations (Hernandez-Lopez et al 2006).


Chronic non-cancer pain: Focus on once-daily tramadol formulations.

Coluzzi F, Mattia C - Ther Clin Risk Manag (2007)

Mean plasma concentration-time profile for racemic tramadol (sum of both enantiomers) after a single oral dose in the fasting state of three different formulations: OD Tramadol Contramid® 200 mg (Labopharm), OD Tramadol 200 mg (Zambon), and OD Tramadol 200 mg (SMB Technology) (Malonne et al 2003; Hernandez-Lopez et al 2006).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376086&req=5

fig1: Mean plasma concentration-time profile for racemic tramadol (sum of both enantiomers) after a single oral dose in the fasting state of three different formulations: OD Tramadol Contramid® 200 mg (Labopharm), OD Tramadol 200 mg (Zambon), and OD Tramadol 200 mg (SMB Technology) (Malonne et al 2003; Hernandez-Lopez et al 2006).
Mentions: Only recently, a randomized controlled trial comparing two different OD tramadol formulations has been published by Hernandez-Lopez et al (2006). This is the first study that compares the bioavailability of a currently marketed OD tramadol formulation 200 mg using an hydrophobic matrix (Zambon, Spain) with the new OD tramadol formulation 200 mg using the Contramid® technology (Labopharm, Canada), both given as a single dose in the fasting state. 24 of 26 subjects were evaluable for the pharmacokinetic analysis of racemic tramadol and racemic O-demethyltramadol. All pharmacokinetic parameters (AUC, Cmax, C24h, and Tmax) were significantly higher for tramadol Contramid® (p < 0.0004), whereas the elimination half-life (T½) was significantly shorter (7.4 vs 14.9 h, p = 0.0001). Following tramadol Contramid® oral administration, mean plasma concentrations maintained a plateau above 200 ng/ml for a long duration (≥12h) from 4 h through 16 h after dose, while for the reference formulation the plasma levels were maintained for only 2 h, from 4 h through 6 h. Mean plasma concentration of tramadol at 24 h were significantly higher after tramadol Contramid® administration (38.9 vs 26.2 ng/ml p = 0.0001). As the confidence intervals fall outside of the range of acceptability for bioequivalence, these formulations cannot be considered bioequivalent. OD tramadol using Contramid® technology seems to have a better controlled-release profile and can be evaluated to be suprabioavailable. Finally, authors compared their results with those obtained by Malonne et al (2004) with the hydrophilic once-daily tramadol formulation 200 mg (SMB Technology, Belgium). When comparing the Tmax, expressed as median (min-max), the following values were observed: OD tramadol Contramid® (Labopharm) 9.0 h (2–16), OD tramadol (Zambon) 4.5 h (2–12), and OD tramadol (SMB Technology) 10 h (6–12) (Figure 1). The hydrophilic formulation (SMB Technology) showed a lag during which no appreciable drug absorption occurs, and the maximum concentration was achieved after about 10 hours, followed by a fast elimination process, similar to the immediate-release formulations. As shown in Figure 1, there was not a plateau in the plasma concentration-time curve. Thus the author concluded that this should be considered a “delayed-release” formulation, whereas the other two (using the hydrophobic matrix and the Contramid® technology, respectively from Zambon and Labopharm) showed pharmacokinetics characteristics of “controlled-release” formulations (Hernandez-Lopez et al 2006).

Bottom Line: New once-daily (OD) formulations of tramadol have been marketed in various countries, in order to offer the advantage of a reduced dosing regimen and to improve patients' compliance.This review focuses on the technology, pharmacology, clinical efficacy, and safety of different once-daily tramadol formulations.Hydrophilic vs hydrophobic matrix systems and newer technologies used in once-daily formulations to control drug delivery are discussed.

View Article: PubMed Central - PubMed

Affiliation: ICOT - Polo Pontino, Rome, Italy; Department of Anesthesia, Intensive Care Medicine and Pain Therapy, University "La Sapienza" Rome, Italy.

ABSTRACT
Despite progress in pain management, chronic non-cancer pain (CNCP) represents still a clinical challenge. The efficacy and safety profile of tramadol make it suitable as a long-term treatment in a variety of CNCP conditions. New once-daily (OD) formulations of tramadol have been marketed in various countries, in order to offer the advantage of a reduced dosing regimen and to improve patients' compliance. This review focuses on the technology, pharmacology, clinical efficacy, and safety of different once-daily tramadol formulations. Hydrophilic vs hydrophobic matrix systems and newer technologies used in once-daily formulations to control drug delivery are discussed. Three randomized controlled trials (RCTs) established OD tramadol analgesic efficacy to be superior to that of placebo for pain management and functional improvement in patients with osteoarthritis. Three RCTs demonstrated similar rates of efficacy between OD tramadol and immediate-release (IR) or sustained-release (SR) formulations, with a better adverse events profile. An open trial on long term tolerability showed that OD tramadol is generally safe in rheumatological pain treatment.

No MeSH data available.


Related in: MedlinePlus