Background: In pharmacokinetics, the Wagner-Nelson (W-N) method can accurately estimate the rate of drug absorption from its urinary elimination rate. A stable isotope (¹³C) breath test attempts to estimate the rate of absorption of ¹³C, as an index of gastric emptying rate, from the rate of pulmonary elimination of ¹³CO₂. The time-gastric emptying curve determined by the breath test is quite different from that determined by scintigraphy or ultrasonography. In this report, we have shown that the W-N method can adjust the difference. Methods: The W-N equation to estimate gastric emptying from breath data is as follows: the fractional cumulative amount of gastric contents emptied by time t = A_breath(t)/A_breath(∞) + (1/0.65)·d[A_breath(t)/A_breath(∞)]/dt, where A_breath(t) = the cumulative recovery of ¹³CO₂ in breath by time t and A_breath(∞) = the ultimate cumulative ¹³CO₂ recovery. The emptying flow curve generated by ultrasonography was compared with that generated by the W-N method-adjusted breath test in 6 volunteers. Results: The emptying curves by the W-N method were almost identical to those by ultrasound. Conclusions: The W-N method can generate an accurate emptying flow curve from ¹³CO₂ data, and it can adjust the difference between ultrasonography and the breath test.

A [13C]-breath test is a promising method for measuring gastric emptying. The methodological relevance is based on a close correspondence between gastric emptying of [13C]-acetate/octanoate (input) and pulmonary excretion of [13CO2] (output). Despite the close input-output correspondence, the pulmonary output is quite remote from the gastric input: the pulmonary output is delayed compared to the gastric input, and the total recovery of [13CO2] in the breath is incomplete. This review focuses on the kinetics of [13C]-acetate/octanoate in the body and suggests that (1) the delayed pulmonary output results from temporal retention of [13CO2] in the well-perfused tissues (heart, brain, etc.), (2) the incomplete recovery results from incorporation of the label into metabolic products (ketone bodies, amino acids, etc.) or from fixation of [13CO2] in the low-perfused tissues (bone, skeletal muscle, etc.), and (3) knowledge on the retention is the key to appropriate interpretations of breath test results. Recognition of these kinetic aspects is essential for appropriate interpretations of these breath test results.

The proton pump inhibitor (PPI) is widely used for the treatment of gastroesophageal reflux disease, peptic ulcer diseases, and functional dyspepsia. The pathogenesis of these acid-related and/or functional upper gastrointestinal disorders is potentially associated with abnormal gastric emptying. To date, variable effects of PPIs on gastric emptying have been reported. Therefore, it is relevant to gather and analyze published information on this topic. A systematic literature search has been performed, showing that the delaying effect of PPIs on gastric emptying of solid meals is consistent, whereas the effect of PPIs on the emptying of liquids is inconsistent. The underlying mechanisms whereby PPIs may affect gastric emptying have been discussed, most of which still remain hypothetic. Gastric emptying of solids involves a process of peptic hydrolysis. PPIs impair the hydrolytic digestion by inhibiting acid-dependent peptic activity, thereby delaying the solid emptying. Gastric emptying of liquids largely depends on volume and energy density of intragastric contents. PPIs variably modify the volume and the energy density by reducing gastric fluid secretion, thereby modifying the liquid emptying in an unpredictable manner. Hypergastrinemia has been considered to delay gastric emptying, but it seems of minor importance in the regulation of gastric emptying during PPI use. The delayed emptying of solids due to PPI therapy may have clinical implications in the management of gastroesophageal reflux disease, functional dyspepsia, as well as diabetes.

The paracetamol absorption technique, a widely used method for evaluating the gastric emptying rate of liquids, appears to be performed inappropriately, resulting from a lack of consideration of pharmacokinetics in paracetamol absorption. This review suggests that appropriate study designs and logical choice of the parameters for the rate of paracetamol absorption are the cornerstone of reliable investigation of gastric emptying using the paracetamol method.

1. The [(13)C]-acetate breath test (ABT) quantifies gastric emptying as the half [(13)CO(2)]-excretion time (T(1/2b)), but T(1/2b) differs from the scintigraphic half-emptying time (T(1/2s)). The aims of the present study were to accurately determine the half-emptying time by ABT with Wagner-Nelson analysis (T(1/2WN)), to compare T(1/2WN) with T(1/2s) and to validate the Wagner-Nelson strategy in ABT. 2. For a comparative study, eight volunteers simultaneously underwent ABT and scintigraphy. Anterior images were acquired and breath samples were collected every 15 min for 4.0 h after ingestion of a 200 kcal liquid meal labelled with 37 MBq [(99m)Tc]-colloidal sulphur and 100 mg [(13)C]-acetate. For the validation experiment, another six volunteers underwent ABT, on two randomized occasions, using the 200 kcal liquid meal with 100 mg [(13)C]-acetate. On either of the two occasions, a gel-forming agent was stirred into the meal to intentionally delay gastric emptying by increasing meal viscosity. Breath samples were collected at regular 15 min intervals for 4 h post ingestion. 3. The Wagner-Nelson equation for ABT is F(t) = (A(breath)(t) + C(t)/0.65)/A(breath)(infinity), where F(t) is a fractional dose of the [(13)C] label emptied, C(t) is the [(13)CO(2)] excretion (% dose/h), A(breath)(t) is the area under the C(t) curve (% dose) and A(breath)(infinity) is the ultimate [(13)CO(2)] recovery in breath (% dose). The percentage gastric retention was estimated as 100 x (1 - F(t)). The time plots of scintigraphic activity and 100 x (1 - F(t)) were fitted to y(t) = 100 x e(-Kxt), K values were estimated mathematically for each plot by regression analysis and T(1/2s) and T(1/2WN) were calculated as (ln2)/K. The time versus pulmonary [(13)CO(2)] excretion plots were fitted to z(t) = m x k x beta x e(-kt)(1 - e(-kxt))(beta-1), where m, k and beta are constants; T(1/2b) was calculated as -(ln(1 - 2(-1/beta))]/k. 4. Values of T(1/2WN) were closer to T(1/2s) than T(1/2b), although T(1/2WN) and T(1/2b) yielded significant under- and overestimation of T(1/2s), respectively. The high viscosity meal significantly prolonged T(1/2WN) and T(1/2b); T(1/2WN) could detect the delayed transit of the viscous meal more sensitively than T(1/2b). 5. The Wagner-Nelson method improves the accuracy of the ABT.