Liquid Enteral Nutrients Alter the Pharmacokinetics of Orally Administered Carbamazepine in Rats

The interaction between enteral nutrients (ENs) and drugs co-administered through a nasogastric (NG) tube reportedly affects the absorption and resultant plasma concentrations of the respective drugs. However, the gastrointestinal absorption of carbamazepine (CBZ), an antiepileptic drug, co-administered with liquid ENs through an NG tube has not been clarified. In this study, we measured the recovery rate (%) of CBZ (Tegretol^® powder) passed through an NG tube when co-administered with distilled water or ENs (F2α^®, Racol^® NF, Ensure Liquid^®, and Renalen^® LP) of different compositions, frequently used in Japan. We also measured the plasma CBZ level in 26 rats after oral co-administration of CBZ with liquid ENs. The CBZ recovery rate was close to 100% in rats of all EN groups after passage through the NG tube. Furthermore, CBZ area under the plasma concentration-time curve from time zero to 9 h (AUC_0→9h) of the Ensure liquid^® group decreased compared with that of control group (P < 0.05) and Renalen^® LP group (P < 0.01). However, the AUC_0→9h of CBZ remained unchanged when co-administered with Ensure liquid^® 2 h after initial CBZ administration. In conclusion, the co-administration of CBZ with Ensure Liquid^® caused a reduction in the absorption of CBZ from the gastrointestinal tract, without adsorption on the NG tube. The administration of Ensure Liquid^® 2 h after CBZ is a way to prevent a decrease in plasma CBZ concentration. Our findings suggest that carefully monitoring the plasma levels of CBZ is necessary in co-administation with Ensure liquid^® to prevent the unintended effects of the interaction between CBZ and liquid EN.