Pharmacokinetic Considerations in Gastrointestinal Motor Disorders

Hebbard, Geoffrey; Sun, Wei; Bochner, Felix; Horowitz, Michael

doi:10.2165/00003088-199528010-00005

Cited by 49 publications

(35 citation statements)

References 210 publications

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“…Delayed gastric emptying in patients with gastroparesis alters glucose absorption and the mismatch between glucose absorption and insulin action results in wide excursions in blood glucose concentrations with MDI regimens [7]. In addition, patients with severe symptomatic gastroparesis are unable to have regular meals and frequently omit their insulin in an attempt to avoid the risk of hypoglycaemia.…”

Section: Discussionmentioning

confidence: 99%

The role of continuous subcutaneous insulin infusion therapy in patients with diabetic gastroparesis

et al. 2011

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Aims/objective To describe the effectiveness of continuous subcutaneous insulin infusion (CSII) in patients with symptomatic diabetic gastroparesis and unstable glycaemic control. Methods Data from 26 patients with symptomatic diabetic gastroparesis and unstable glycaemic control using multiple-dose insulin (MDI) regimens, and subsequently managed with CSII, were analysed. Results Following initiation of CSII, the median length of inpatient bed days associated with hospital admissions related to gastroparesis and glycaemic instability was reduced from 8.5 (range 0-144) days patient −1 year −1 prior to CSII to 0 (range 0-15) days patient −1 year −1 .The median HbA 1c reduction with CSII was 1.8% (22 mmol/mol; p<0.05). The median capillary blood glucose (CBG) with CSII was significantly lower than with MDI: 7.7 mmol/l (range 3.8-15.4 mmol/l) vs 9.8 mmol/l (range 2.3-27 mmol/l), respectively, p<0.001. Glycaemic variability with CSII was significantly reduced compared with MDI: CBG CV 0.37 vs CV 0.53, respectively, p<0.001. Conclusions/interpretation CSII therapy in patients with diabetic gastroparesis results in significant improvement in glycaemic control and reductions in glycaemic variability and number of hospital inpatient bed days.

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Section: Discussionmentioning

confidence: 99%

The role of continuous subcutaneous insulin infusion therapy in patients with diabetic gastroparesis

et al. 2011

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“…The delay of gastric emptying by ingested foods was also reported to cause the delay of the absorption of several drugs, including theophylline in human. 52,53) The analysis using GITA Model and gamma scintigraphic technique made it possible to estimate the variable absorption kinetics regulated by the GI transit with a huge variability. The plasma concentration-time profile of theophylline after oral administration in human volunteers was predicted using the individual GI transit data monitored by a gamma scintigraphic technique.…”

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confidence: 99%

Gastrointestinal Transit and Drug Absorption

Kimura

Higaki

2002

Biological & Pharmaceutical Bulletin

169

114

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Oral drug administration is the most convenient and common for drug therapy and it is, therefore, very important and useful to estimate the absorbability of drugs and to predict the plasma concentration profile of drugs after oral administration for the development of novel drugs and/or novel dosage form and the designation of the dosage regimen. Generally, the absorbability of drugs has been estimated by in-situ recirculation studies, in-situ closed loop studies or the analysis by the simple compartment model. The information which can be obtained from these approaches is usually an absorption rate constant, ka. The ka value is generally the averaged one throughout the intestinal tract. However, there is the site-difference in drug absorbability [1][2][3][4] and variable residence time of drugs in each segment must make the contribution of each segment to drug absorption changed, resulting in the different absorbability as a whole. As for the drug absorption after oral administration, the gastrointestinal (GI) transit of a drug is also an important factor to determine the drug absorption and is so variable, as was influenced by not only individual differences, 5) but also the dosage conditions like meals, 6) disease states 7) and so on. Therefore, the absorbability and the residence time in each segment are the major determining factors for drug absorption after oral administration and very important for the analysis of drug absorption kinetics and the estimation of, and the prediction of plasma concentration profiles of drugs. However, the analysis and the estimation of drug absorption after oral administration have been usually performed by a simple compartment model, where even a process of gastric emptying is not included often. This kind of simple model cannot describe the irregular shape in the plasma concentration, which is often observed. Therefore, several models were proposed to analyze the plasma profile, [8][9][10][11] but they are not necessarily based on the practical phenomena, i.e. GI transit and site-different drug absorbability.We have developed a GI-Transit-Absorption (GITA) Model containing the GI transit and absorption processes to analyze and predict the plasma concentration profile after oral administration of aqueous drug solution.12) Although several efficient methods to estimate the absorption of orally administered drug by analyzing the GI disposition following oral administration (GI disposition analysis) have been reported, some are only focused on the gastric emptying based on a model having a stomach and an intestine compartment. 13,14) The other one estimated the intestinal transit of a drug using polyethylene glycol 4000 as a nonabsorbable marker, 10) but the actual data of intestinal transit were not utilized enough to analyze and predict the drug absorption kinetics. Although the analytical procedures for plasma profile of a drug absorbed from successive absorption sites along the GI tract have been also reported, [16][17][18] they just showed the concept and/or simulation stu...

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“…2 For some medicines, this can be associated with a withdrawal or discontinuation syndrome (see Table), 3,4 which is predictable and potentially avoidable. This is a particular concern with shorter acting drugs in a controlledrelease formulation (which depends on normal gut transit time) when the decrease in plasma concentration reduces the patient's functional status (e.g.…”

Section: Controlled-release Formulationsmentioning

confidence: 99%