Assessing the Impact of Postural Restriction on the Pharmacokinetics of Mebendazole in Healthy volunteers

Abstract

Introduction: Mebendazole, a BCS Class II drug, demonstrates poor aqueous solubility and variable systemic absorption. While the impact of food on its pharmacokinetics is well established, the influence of postural restriction on its absorption remains unclear.

Objectives

To evaluate whether maintaining a seated, upright posture after dosing alters the pharmacokinetics of mebendazole administered under fed conditions in healthy volunteers.

Methods: A randomised, open-label, two-period crossover study was conducted in 24 healthy volunteers. Each subject received a single 500 mg dose of mebendazole under fed conditions, either with four hours of seated postural restriction or without any restriction. Plasma concentrations were quantified using a validated LC-MS/MS method. Pharmacokinetic parameters including C_max, AUC_0–t, T_max, t½, and Kel were calculated and compared using the Wilcoxon signed-rank test.

Results: Postural restriction showed a non-significant trend towards higher C_max (79.35 ± 55.17 vs. 73.30 ± 39.70 ng/mL; p=0.603) and AUC_0–t (480.92 ± 72.67 vs. 465.95 ± 73.73 ng·h/mL; p=0.900). T_max, t½, and Kel was comparable across conditions. The findings suggest that posture exerts minimal influence on mebendazole pharmacokinetics under fed conditions.

Conclusions:

Postural restriction has limited impact on mebendazole pharmacokinetics. Clinical emphasis should remain on dietary factors, particularly co-administration with high-fat meals, rather than postural adjustments.