The effect of metoclopramide and atropine on the absorption of orally administered mexiletine

The effect of pretreatment with intravenous metoclopramide (10 mg) and atropine (0.6 mg), both separately and combined, on the absorption rate and relative oral bioavailability of the antiarrhythmic drug, mexiletine (400 mg) was studied in eight fasting healthy males using a Latin Square design for order of pretreatment administration. The time (Tmax) of the maximum mexiletine plasma concentration (Cpmax) was reduced by metoclopramide (P < 0.001) and was increased by atropine (P < 0.01) compared with saline control. Tmax was not significantly altered by combined metoclopramide and atropine pretreatment. Atropine pretreatment was associated with a significant reduction of Cpmax (P < 0.05) and of elimination half-life (P < 0.05). The area under the mexiletine plasma concentration-time curve was not affected by any of the pretreatments. The results suggested that metoclopramide enhanced and atropine decreased the rate of mexiletine absorption without altering the relative oral bioavailability. When the pretreatments were administered in combination, metoclopramide reversed the delay in mexiletine absorption produced by atropine.