Pharmacokinetic and pharmacodynamic properties of tramadol IR and SR in elderly patients: a prospective, age-group-controlled study.

BACKGROUND

Tramadol is widely prescribed, even to the eldest patients. Although age-related differences in pharmacologic responsiveness are to be expected, the pharmacodynamic and pharmacokinetic (PK) properties of tramadol have not been systematically compared between patients of various ages.

OBJECTIVE

The aim of this study was to explore the effectiveness, PK properties, and safety profile of 2 galenic tramadol formulations in 3 similarly sized age groups with malignant and nonmalignant pain of moderate to severe intensity.

METHODS

This prospective, age-group-controlled study was conducted at the ambulatory pain clinic of the Landeskrankenhaus Kärnten, Klagenfurt, Austria. Male and female adults with malignant and nonmalignant pain of moderate to severe intensity were eligible. Patients were stratified into similarly sized age groups, as follows: >or=75, 65-<75, and <65 years. Patients first received the immediate-release galenic formulation of tramadol (tramadol IR) until steady state was achieved, followed by the sustained-release formulation (tramadol SR) until steady state. Serum concentrations of tramadol and its active metabolite (O-desmethyl-tramadol [M1]) were measured using gas chromatography to estimate the age-related PK handling of the analgesic drug. Three validated scales were used to measure pain intensity during the study: a 100-mm visual analog scale (VAS), an 11-point numeric analog scale (NAS), and a 4-point verbal rating scale (VRS). Tolerability was assessed by evaluating daily answers about the potential occurrence of adverse events (and respective details such as type and severity) from baseline until the end of the observation period.

RESULTS

A total of 100 patients were enrolled (58 women, 42 men; mean [SD] age, 65.2 [15.0] years; >or=75, 30 patients; 65-<75, 31 patients; and <65 years, 39 patients). Predominant causes of pain were neoplasms (27.4% of causes) and injury and other external causes (20.8%), and diseases of the musculoskeletal and connective-tissues systems (19.8%). Fifty-five patients completed the study and provided all data as planned. Mean (SEM) steady-state tramadol IR doses were 250 (20.2), 277 (39.8), and 325 (33.1) mg/d in patients aged >or=75, 65-<75, and 65 years, respectively (P = NS); tramadol SR, 278 (27.5), 306 (39.7), and 340 (35.1) mg/d (P = NS). Serum concentrations of tramadol and M1 were statistically similar across all 3 age groups. Overall, mean pain intensity scores, as measured using the VAS and NAS, were decreased from baseline (62.4 [2.0] mm and 6.22 [0.22] points, respectively) to steady state with tramadol IR (23.6 [2.9] mm and 2.65 [0.30] points) and tramadol SR (16.9 [2.5] mm and 1.91 [0.26] points) (all, P < 0.001). Pain intensity before and improvements during both treatment phases were similar across all 3 age groups.

RESULTS

for pain intensity on the VRS also did not find age-related differences. The predominant adverse effects were nausea (27.0% of patients), dizziness and giddiness (18.0%), and malaise and fatigue (15.0%); no significant differences in adverse events were found between age groups.

CONCLUSIONS

The fate of tramadol and its active metabolite, and their clinical effects, have been examined here for the first time in a prospective cohort study, which compared patients aged <65 years, 65-<75 years, and >or=75 years. In contrast to expectations, it was concluded that tramadol IR and tramadol SR were both generally well tolerated and effective in the treatment of moderate to severe pain in any of the 3 age groups in these patients. Although the eldest group of patients consumed, on average, 20% less tramadol (P = NS) than the youngest group, the PK properties of both drugs were not changed when given to elderly patients.