The stimulation of antral motility by erythromycin is attenuated by hyperglycemia.
OBJECTIVE
Diabetic gastroparesis is usually treated with prokinetic drugs, of which the most potent, when given intravenously during euglycemia, is erythromycin. Recent studies have demonstrated that the gastrokinetic effects of erythromycin are attenuated by hyperglycemia. The aim of this study was to determine whether the effects of erythromycin on antropyloroduodenal motility, including the organization of antral pressure waves, are modified by hyperglycemia.


METHODS
A total of eight healthy male volunteers (median age 24 yr) were studied on 2 days each in randomized order. A manometric assembly, incorporating six antral, two pyloric, and seven duodenal sideholes and a pyloric sleeve sensor, was positioned with the sleeve spanning the pylorus. The blood glucose concentration was stabilized at about 5 mmol/L (euglycemia) or 15 mmol/L (hyperglycemia). After 30 min (T = 0), an intraduodenal lipid infusion (1.5 kcal/min) was commenced and continued until the end of the study. At T = 20 minutes, erythromycin (200 mg) as the lactobionate was infused intravenously over 20 min, followed by 100 mg over the next 40 min.


RESULTS
Intravenous erythromycin increased the amplitude of antral waves during intraduodenal lipid infusion at both blood glucose concentrations (p < 0.01 for euglycemia and p < 0.05 for hyperglycemia). After erythromycin (T = 20 to T = 80), the frequency (p < 0.05) and amplitude (p < 0.01) of antral waves were less during hyperglycemia than euglycemia. Both propagated (p < 0.0005) and nonpropagated (p < 0.01) antral waves were decreased by hyperglycemia, but the suppression of propagated waves was greater (p < 0.05). Erythromycin reduced the frequency (p = 0.09) but increased the amplitude (p < 0.05) of phasic pyloric pressures, and decreased basal pyloric pressure (p < 0.0005). The frequency (p = 0.06) and amplitude (p < 0.05) of phasic pyloric waves during erythromycin infusion were slightly less during hyperglycemia than euglycemia, whereas there was no effect of the blood glucose concentration on basal pyloric pressure. Erythromycin increased the amplitude (p < 0.001) but not the frequency of duodenal waves; the frequency and amplitude of duodenal waves did not differ between the two blood glucose concentrations.


CONCLUSIONS
Hyperglycemia attenuates the stimulation of antral pressures and propagated antral sequences by erythromycin, but not the effects of erythromycin on pyloric or duodenal motility.
Rayner
C K
CK
University of Adelaide Department of Medicine, Royal Adelaide Hospital, Australia.
Su
Y C
YC
Doran
S M
SM
Jones
K L
KL
Malbert
C H
CH
Horowitz
M
M
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004187:Disaccharides / Q000008:administration & dosage; D004386:Duodenum / Q000187:drug effects / Q000503:physiopathology; D004917:Erythromycin / Q000008:administration & dosage*; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology; D005765:Gastrointestinal Agents / Q000008:administration & dosage*; D018589:Gastroparesis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D008365:Manometry; D011312:Pressure; D011706:Pyloric Antrum / Q000187:drug effects / Q000503:physiopathology*; D012016:Reference Values
D001786:Blood Glucose; D004187:Disaccharides; D005765:Gastrointestinal Agents; D004917:Erythromycin; C005608:lactobionic acid