Synergistic relaxing effect of the paracetamol and pyrilamine combination in isolated human myometrium

Abstract

Objective: To evaluate the interaction type of the human uterine relaxant effect of the paracetamol-pyrilamine combination (PPC) in vitro.

Study design: Uterine strips were contracted with KCl (60 mM) and treated with vehicle or increasing concentrations of paracetamol (100-3200 μM), pyrilamine (3.2-100 μM) or the PPC. The relaxing effects of the drugs alone and in combination were measured. Isobolographic analysis was used to determine the pharmacologic interaction type.

Results: Paracetamol, pyrilamine and the PPC produced a significant relaxing effect on non-pregnant human uterine strips pre-contracted with KCl (60 mM). The EC30 values for paracetamol and pyrilamine on the uterine contraction were 2391.3±595.3 μM and 14.7±1.7 μM, respectively. The derived experimental EC30 for the PPC was 401.8±129.8 μM. This value was significantly lower (p<0.05) than the theoretical EC30 expected for a purely additive interaction, which was 1203.0±297.7 μM for the PPC. The interaction index (γ) was 0.33±0.14 for PPC, being statistically different from unity.

Conclusion: Data suggest that low doses of the PPC can interact synergistically and therefore this drug association may represent a therapeutic advantage for the clinical treatment of dysmenorreic pain.