Sequential single doses of cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: a randomized, placebo-controlled, crossover study.

OBJECTIVE: To evaluate the comparative efficacy of enteral cisapride, metoclopramide, erythromycin, and placebo for promoting gastric emptying in critically ill patients with intolerance to gastric enteral nutrition (EN). DESIGN: A randomized, crossover study. SETTING: Adult medical intensive care unit at a university-affiliated private hospital and trauma intensive care unit at a university teaching hospital. PATIENTS: Ten adult, critically ill, mechanically ventilated patients not tolerating a fiber-containing EN product defined as a single aspirated gastric residual volume >150 mL or two aspirated gastric residual volumes >120 mL during a 12-hr period. INTERVENTIONS: Patients received 10 mg of cisapride, 200 mg of erythromycin ethylsuccinate, 10 mg of metoclopramide, and placebo as 20 mL of sterile water every 12 hrs over 48 hrs. Acetaminophen solution (1000 mg) was administered concurrently. Gastric residual volumes were assessed, and plasma acetaminophen concentrations were serially determined by TDx between 0 and 12 hrs to evaluate gastric emptying. MEASUREMENTS AND MAIN RESULTS: Gastric residual volumes during the study were not significantly different between agents. No differences in area under the concentration vs. time curve or elimination rate constant were identified between agents. Metoclopramide and cisapride had a significantly shorter mean residence time of absorption than erythromycin (6.3+/-4.5 [SEM] mins and 10.9+/-5.8 vs. 30.1+/-4.5 mins, respectively [p<.05]). Metoclopramide (9.7+/-15.3 mins) had a significantly shorter time to peak concentration compared with erythromycin and placebo (60.7+/-8.1 and 50.9+/-13.5 mins, respectively [p<.05]). The time to onset of absorption was significantly shorter for metoclopramide vs. cisapride (5.7+/-4.5 vs. 22.9+/-5.7 mins [p<.05]). CONCLUSION: In critically ill patients intolerant to EN, single enteral doses of metoclopramide or cisapride are effective for promoting gastric emptying in critically ill patients with gastric motility dysfunction. Additionally, metoclopramide may provide a quicker onset than cisapride.

Differences between blacks and whites in plasma protein binding of drugs.

OBJECTIVE: Disopyramide and salicylic acid were used as model compounds to characterize racial differences in binding of drugs by alpha 1-acid glycoprotein (AGP) and albumin, respectively. Drug-free plasma was collected from 29 healthy volunteers (15 white, 14 black). Disopyramide and salicylic acid unbound fractions (fu) in plasma were determined by equilibrium dialysis using 14C-disopyramide and 14C-salicylic acid. RESULTS: Disopyramide unbound fractions were significantly higher in blacks than whites (0.131 vs 0.113) as were salicylic acid unbound fractions (0.053 vs 0.048). When unbound fractions were corrected for AGP and albumin concentration, racial differences were no longer present. CONCLUSION: Many drugs which bind to AGP and/or albumin may exhibit racial differences in unbound fractions. However, these differences are likely explained by differences in protein concentrations rather than differences in the number of binding sites on the protein or racial differences in affinity of the protein for drugs.