Effects of concurrent and staggered dosing of semi-solid enteral nutrients on pharmacokinetic behavior of antiepileptic drugs after oral administration in rats

Background The use of enteral nutrients plays a highly important role in accurate nutrition management, but limited information is currently available on the cautionary points of semi-solid enteral nutrients. Aim In this study, we examined whether the pharmacokinetic profiles of sodium valproate (SVA), levetiracetam (LEV), and carbamazepine (CBZ) are affected by altering the dosing time of RACOL®-NF Semi Solid for Enteral Use (RASS), a prescribed semi-solid formula. We also investigated whether the pharmacokinetic interaction observed in this study can be avoided by staggered dosing of the chemical drug and semi-solid enteral nutrient. Methods The plasma concentration of SVA, LEV and CBZ after oral administration was measured by LC-MS/MS method. Results There was no difference in pharmacokinetic characteristics of SVA and LEV when the dosing time of RASS was altered. On the other hand, the plasma concentration of CBZ after oral administration at all sampling points decreased with the extension of the dosing time of RASS, which was consistent with the Cmax and AUC. However, no significant difference was observed in the pharmacokinetic profiles or parameters of CBZ between the short-term and long-term RASS dosing groups by prolonging the administered interval of CBZ and RASS for 2 hr. Conclusion We concluded that the pharmacokinetic profiles of CBZ, but not SVA and LEV, after its oral administration are affected by the dosing time of RASS, but staggered administration of CBZ and RASS prevented their interaction.

Endoscopic Insertion of Nasojejunal Feeding Tube at Bedside for Critically Ill Patients: Relationship between Tube Position and Intragastric Countercurrent of Contrast Medium

Background and Oblectives: We evaluated the success rate of endoscopically positioned nasojejunal feeding tubes and the intragastric countercurrent of contrast medium thereafter. Method: This retrospective observational study investigated patients who were admitted to a single intensive care unit and required endoscopic placement of a post-pyloric feeding tube between January 2010 and June 2016. The feeding tube was grasped with forceps via a transoral endoscope and inserted into the duodenum or jejunum. Thereafter, we assessed the position of the tube and the intragastric countercurrent using abdominal radiography with contrast medium. Results: The tube tip was inserted at the jejunum and the duodenal fourth portion in 55.8 and 33.6% of patients, respectively. The tip of the inserted tube had moved into the jejunum of 71.7% of patients by the following day. The countercurrent rate was significantly lower among patients with a tube inserted into the duodenal fourth portion or more distal than among those with tubes inserted more proximally (8.4 vs. 45.4%, p = 0.0022). Conclusions: The endoscopic insertion and positioning of a nasojejunal feeding tube seemed effective because the rate of tube insertion into the duodenal fourth portion or more distal was about 90%. The findings of intragastric countercurrents indicated that feeding tubes should be inserted into the duodenal fourth portion or beyond to prevent vomiting and the aspiration of enteral nutrients.

Alterations in Pharmacokinetics of Orally Administered Carbamazepine in Rats Treated with Sodium alginate: Possible Interaction between Therapeutic Drugs and Semi-solid Enteral Nutrients

Objective The use of enteral nutrients plays an extremely important role in accurate nutrition management. Sodium alginate (SA) is frequently used for the semi-solidification of enteral nutrients. In the present study, we investigated whether the pharmacokinetic profile of orally administered carbamazepine (CBZ) is altered by a treatment with SA immediately before and after dosing of the drug. Furthermore, the adsorption effects of SA on CBZ were examined using an in vitro analysis. Method SA was orally administered to rats just before and immediately after CBZ dosing. The CBZ concentration profile following its oral administration was analyzed by a non-compartmental method. The adsorption of CBZ onto SA was evaluated after centrifugation using an ultrafiltration device. Findings The serum concentration of orally administered CBZ at each sampling point was reduced by the treatment with SA, and the extent of the decrease observed in the concentration of CBZ was larger when SA was ingested immediately after administration of the drug, which was consistent with the alteration observed in the value of the area under the curve (AUC). No significant differences were noted in the elimination rate at the terminal phase (ke) among the groups. In the in vitro assay, CBZ was adsorbed by SA in the solution used to reflect fluid in the intestinal tract. Conclusions The pharmacological efficacies of CBZ might be reduced by SA through the pharmacokinetic interactions, and that the careful attention should be paid to the timing of administration of CBZ and semi-solid enteral nutrients.