Tramadol SR Formulations : Pharmacokinetic Comparison of a Multiple-Units Dose (Capsule) versus a Single-Unit Dose (Tablet).
BACKGROUND
Different oral sustained-release (SR) formulations of tramadol have been introduced in pain treatment in order to prolong the dosage interval to improve convenience for the patient. The objective of this study was to compare tramadol pharmacokinetics and intra- and intersubject variability after replicate single-dose administrations of a multiple-units SR formulation (capsule) and a single-unit formulation (tablet).


METHODS
This was a randomised, single-dose, single-centre study with an open-label, four-period, two-sequence, two-formulation, replicate crossover design in healthy subjects under fed conditions. The main outcome measures were the intra- and intersubject variance of the area under the concentration-time curve from 0 to 12 hours (AUC(12)) and maximum concentration (C(max)), as well as the mean AUC(12) and C(max) for tramadol. Study drugs were a tramadol SR multiple-units formulation (capsule) and a tramadol SR single-unit formulation (tablet), each containing tramadol hydrochloride 100mg. The time interval from 0 to 12 hours of AUC(12) of the single-dose design corresponds to the recommended twice-daily dosage interval for both study drugs during long-term treatment.


RESULTS
The two formulations were equivalent in the area under the curve (AUC(infinity): 2411 vs 2527 mug . h/L). However, capsules led to a lower C(max) (148.6 vs 183.2 mug/L), to a later time to reach C(max) (5.9 vs 4.9 hours), and to a longer half-value duration (13.4 vs 10.4 hours). In addition, intrasubject variability of AUC(12) was significantly smaller for capsules than for tablets (p = 0.041). Capsules also produced smaller intra- and intersubject variability in plasma concentrations during the first 2.5 and 3.0 hours after administration, respectively (p < 0.05).


CONCLUSIONS
Although tramadol SR capsules and tramadol SR tablets led to an equivalent systemic exposure to the drug, capsules provided a smoother and more extended plasma profile. In addition, in the case of capsules, bioavailability was subjected to lower variability in terms of both rate and extent of absorption.
Cnota
Peter J
PJ
Scientific Affairs Clinical Research, VIATRIS GmbH & Co. KG, Bad Homburg, Germany.
Nowak
Horst
H
Tagarro
Ignacio
I
Erb
Katharina
K
Schürer
Michael
M
Schulz
Hans-Ulrich
HU
Maus
Joachim
J