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Propantheline Gut 1994; 35: 333-337 333 Pharmacological modulation ofgastric emptying rate of solids as measured by the carbon labelled octanoic acid breath test: influence of erythromycin and Gut: first published as 10.1136/gut.35.3.333 on 1 March 1994. Downloaded from propantheline B D Maes, M I Hiele, B J Geypens, P J Rutgeerts, Y F Ghoos, G Vantrappen Abstract process, the rate of *CO2 excretion in the breath The *C (13C or 14C) labelled octanoic acid as a function of time can be used to measure the breath test was recently developed to measure gastric emptying rate. In a validation study, with the gastric emptying rate of solids. This study simultaneous radioscintigraphic and breath test aimed to investigate whether it is sensitive measurements, an excellent correlation was enough to detect pharmacologically induced found between the gastric emptying results of changes in the gastric emptying rate. Nine the radioscintigraphic method (lag phase, half healthy volunteers were studied in basal condi- emptying time) and those of the breath test (lag tion, after intravenous administration of 200 phase, half emptying time, and the gastric mg erythromycin, and after peroral adminis- emptying coefficient) when using a solid tration of 30 mg propantheline. Erythromycin standard test meal of 250 kcal. The breath test significantly enhanced gastric emptying in all was both sensitive and specific when discriminat- subjects, with an increase ofthe gastric empty- ing between normal and delayed gastric empty- ing coefficient (p=00043) in eight ofnine and a ing.17 fall in both the gastric half emptying time In this study, we wanted to investigate the (p=00020) and the lag phase (p=00044) in sensitivity ofthe *C labelled octanoic acid breath all nine. Propantheline significantly reduced test in measuring even minor drug induced the gastric emptying rate, with a decreased changes in the gastric emptying rate of solids in gastric emptying coefficient (p=0 0007) and individual healthy volunteers. Two drugs with a an increased gastric half emptying time known influence on gastrointestinal motor no were used - erythromycin, which (p=00168) in all subjects, but change in the activity http://gut.bmj.com/ lag phase (p=0.1214). Further mathematical accelerates,'3 and propantheline, which delays analysis showed that breath sampling at 15 gastric emptying. 12 22-23 minutes intervals over a four hour period is recommended to guarantee accuracy and the discriminative value of the breath test in Methods various gastric emptying patterns. In conclu- test SUBJECTS sion the *C labelled octanoic acid breath is on October 2, 2021 by guest. Protected copyright. sufficiently sensitive to show pharmacologic- Nine healthy volunteers (five men and four ally induced changes of gastric emptying rates women; mean age 22 years, range 18 to 25 years) of solids. were studied. None had a history of gastro- (Gut 1994; 35: 333-337) intestinal disease or surgery, or was taking any medication. The gastric emptying rate of a solid standard meal was measured by means of the '4C Gastric emptying is susceptible to a wide variety octanoic acid breath test. of external influences,' including drugs.8 '3 Each subject was studied on three consecutive Care should be taken when interpreting gastric days in three different randomly applied test emptying studies in patients taking drugs with a situations - without medication, 30 minutes after long biological half-life. On the other hand, intravenous administration of200 mg oferythro- Department of Medicine, gastrointestinal side effects of some drugs may mycin (erythromycin lactobionate, Abbott) in Division of prove to be of interesting clinical value, as was 250 ml of NaCl 0-9% over a 15 minute period, Gastroenterology and some and 60 minutes after administration of 30 Gastrointestinal recently shown for macrolide anti- peroral Research Centre, biotics. 1-116 mg of propantheline (propantheline bromide, University Hospital A *C ("3C or 14C) octanoic acid breath test was Continental Pharma). Gasthuisberg, B-3000 to measure the empty- Leuven, Belgium recently developed gastric B D Maes ing rate of solids."' *C octanoic acid, a medium M I Hiele chain fatty acid, is readily solubilised in egg yolk. MATERIALS B J Geypens When cooked as an omelette it has proved to be All tests were carried out after an overnight fast. P J Rutgeerts Y F Ghoos as good a marker of the solid phase of a meal as The test meal consisted of two slices of white G Vantrappen the radioscintigraphic markers for gastric bread and an egg, the yolk of which was doped Correspondence to: emptying studies.'7 Once the egg yolk reaches with 2 ,tCi of 14C octanoic acid, sodium salt Professor Dr G Vantrappen, the (DuPont, NEN Reserarch, Boston, MA, USA). Department of Medicine and the duodenum, rapid disintegration of label- Medical Research, University led solid phase occurs with subsequent absorp- The egg yolk and white were cooked separately Hospital Gasthuisberg, B-3000 to avoid incorporation of octanoic acid into the Leuven, Belgium. tion and preferential hepatic oxidation of *C 820 structure of the white. All meals were Accepted for publication octanoic acid to *CO2.' Since gastric emptying protein 26 July 1993 of the meal is the rate-limiting step in the whole consumed within a five minute period. The 334 Maes, Hiele, Geypens, Rutgeerts, Ghoos, Vantrappen subjects were allowed to drink 150 ml of water decolouration of the indicator. After decoloura- immediately after consuming the meal. The tion, 10 ml of scintillation cocktail (Hionic caloric value of the meal was 250 kcal. Fluor, Packard) were added and radioactivity was determined by liquid scintillation spectro- metry (Packard Tri-Carb Liquid Scintillation Gut: first published as 10.1136/gut.35.3.333 on 1 March 1994. Downloaded from MEASURING TECHNIQUES Spectrometer, model 3375, Packard Instru- Breath samples were taken before the meal, at ments Inc, Downers Grove, IL, USA). CO2 three minute intervals for a period of90 minutes, production was assumed to be 300 mmol/m2 and at 30 minute intervals from 90 to 240 body surface area per hour. Body surface area minutes after ingestion of the meal. At each was calculated using the weight-height formula sampling point, the subjects exhaled into a liquid of Haycock et al.2' The results were expressed as scintillation vial containing 2 ml of 1 M hyamine the percentage of 14C recovery per hour. hydroxide and 2 ml of ethanol together with 1 drop of thymolphthalein solution. This amount oft hyamine is neutralised by 2 mM of C02. The MATHEMATICAL AND STATISTICAL ANALYSIS OF en(d point of neutralisation is indicated by THE RESULTS The mathematical analysis of test results is described in a previous paper.' Briefly, the Figure 1: Results of*C 1 00 A Erythromycin curves with the measured *CO2 recovery in octanoic acid breath test in a as percentage excretion per typical case. (B) represents a breath, expressed normal gastric emptying hour of the given *C dose, were fitted by two pattern, (A) the pattern after 10*00 mathematical formulas as follows: (a) y=atbe-Ct, admtnistration of U) where y is the percentage of *C excretion in erythromycin, and (C) the 0 pattern after administration 'a breath per hour; t is the time in hours; and a, b ofpropantheline. 5*00- and c are regression estimated constants and (b) y=mkpe-kt (1 -e-kt-1), where y is the percent- 0o00.- age of*C excretion in breath per hour; t is time in 0.00 1.00 2.00 3.00 4.00 hours; and m, k, and ,3 are regression estimated Time (h) constants with m the cumulative *C recovery 00 B Normal when time is infinite. The results of this non- linear regression analysis (SAS: PROC NLIN (24) or EXCEL) allows calculation of three 10 00 U) , -<distinctive parameters describing the gastric cn 0 emptying rate of solids, that is: (1) the gastric -a half time 5.00 v > emptying (t½,/b=[60(-1/k)ln(1-2(-"") http://gut.bmj.com/ -66]/I112) in minutes, (2) the lag phase as defined by Siegel (tlagb=[60(lnP)/k-66]/094) in o.00 oo ( 8 @ "minutes and, (3) the gastric emptying coefficient 0.00 1.00 2.00 3.00 4.00 (GEC=ln(a)). Time (h) In each subject, the gastric half emptying 15 00 C Propantheline time, lag phase, and gastric emptying coefficient after erythromycin and after propantheline were compared with the values obtained in the control on October 2, 2021 by guest. Protected copyright. -C 10-00 t tests U)a) ,¢B5Xstudyusing paired comparisons (SAS: 0 PROC MEANS (24)). -0In- 5-00 .SgF To determine the minimum frequency of Figure 2: Mean values of breath sampling needed to achieve accurate "'CO2 excretion for the nine subjects in the nornal information about the gastric emptying rate, situation, after 1.00 2.00 3.00 400 erythromycin, and after 0.00o followingmathematicalsamplingcurve intervals:fitting wassix,repeatednine, for12, the15 propantheline, with the Time (h) and 30 minutes. The calculated gastric half mathematicalfitted curves (solid lines). emptying time, lag phase, and gastric emptying coefficient of these five different sampling fre- quencies were compared with the corresponding values obtained by sampling at three minute intervals using paired comparisons t tests (24). Mr Results U) Figure 1 illustrates a typical 14Co2 breath excre- -o0 tion pattern in a subject studied in three test -o situations - (B) without medication, (A) after Normal \ erythromycin and, (C) after propantheline. The After erythromycin drugs clearly affect the shape of the '4Co2 After propantheline 0 excretion curve representing the percentage of the dose excreted per hour. Erythromycin increases not only the peak but also the slope of I I the ascending and descending limb of l'CO2 0.00 1.00 2.00 3.00 4.00 excretion curve.
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