Efficacy of Tramadol for Pain Management in Patients Receiving Strong Cytochrome P450 2D6 Inhibitors.

STUDY OBJECTIVE: Tramadol is metabolized by cytochrome P450 (CYP) 2D6 to form an active metabolite that exhibits its analgesic effect. Medications that inhibit this enzyme are used often in practice, yet the clinical impact of this interaction on the analgesic effects of tramadol has yet to be fully described. The objective was to determine whether a clinically relevant decrease in pain control is observed in patients taking scheduled tramadol concomitantly with a strong CYP2D6 inhibitor. DESIGN: Retrospective cohort study. SETTING: Large health care system. PATIENTS: One hundred fifty-two adult inpatients who received scheduled tramadol for at least 24 hours with (76 patients) or without (76 patients) a strong CYP2D6 inhibitor between January 1, 2012, and February 28, 2017, were included in the analysis. Patients hospitalized for opioid use disorder or those receiving substandard dosing of tramadol were excluded. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mean breakthrough opiate consumption in the presence and absence of CYP2D6 inhibitors. Secondary outcomes included mean pain scores, length of hospital stay, tramadol discontinuation rates, and prespecified subgroup analyses based on patient sex, race, and specific CYP2D6 inhibitor administered. Patients receiving concurrent CYP2D6 inhibitors required significantly more breakthrough morphine milligram equivalents per day compared with patients receiving scheduled tramadol without CYP2D6 inhibitors (geometric mean ± SD 18.2 ± 6.3 vs 5.7 ± 6.7 mg morphine milligram equivalents, p<0.001). No significant differences existed between cohorts for mean pain score, length of hospital stay, or tramadol discontinuation rate. CONCLUSION: This study demonstrated a clinically relevant decrease in the efficacy of tramadol when used for pain control in patients receiving a strong CYP2D6 inhibitor. These results should encourage clinicians to review medication lists for this interaction and adjust regimens accordingly to ensure adequate pain control.

Bactericidal Peptidomimetic Polyurethanes with Remarkable Selectivity against Escherichia coli.

The increasing incidence of drug-resistant strains of bacteria necessitates the development of new classes of antimicrobials. Host defense peptides, also known as antimicrobial peptides, are promising in this regard but have several drawbacks. Herein, we show that peptidomimetic polyurethanes with pendant functional groups that mimic lysine and valine amino acid residues have high antibacterial activity against Gram negative Escherichia coli, yet are less effective against Gram positive Staphylococcus aureus. All the polyurethanes designed in this study display high bactericidal activity against E. coli, whereas the polyurethanes with high concentrations of lysine mimicking functional groups display minimal cytotoxicity toward mammalian cells. Control experiments with pexiganan, an analogue of the host defense peptide magainin, showed that the polyurethanes described here have high bactericidal activity, while having comparable hemocompatibility and lower mammalian cell toxicity. Overall, the results point to an encouraging new class of peptidomimetic synthetic polymers with selective bactericidal activity to E. coli and low mammalian cell toxicity.