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Meta-analysis of Oro-cecal Transit Time in Fasting Subjects

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Abstract

Purpose

Computer simulations are utilized during pharmaceutical development in order to design appropriate formulation based on the absorption, distribution, metabolism, and excretion (ADME) and physicochemical properties of target compounds, so that adequate prescriptions are offered to patients. Oro-cecal transit time (OCTT) is an important factor affecting these simulations because the absorption of drug that administered orally and the resultant pharmacokinetic profile are expressed as a function of time. Given the large intra- and inter-individual variance in OCTT, it is unsurprising that an accurate model has not yet been proposed.

Methods

We conducted a meta-analysis using subject-level data to construct a statistical model that predicted OCTT. Literature that utilized lactulose to measure OCTT was identified and analyzed using a mixed-effects model.

Results

The OCTTs of fasting healthy subjects were expressed using a linear model, with the amount of lactulose as the single significant explanatory factor. We found that this model could statistically distinguish the OCTTs of subjects with altered physical status from those of healthy people. Specifically, cystic fibrosis and celiac disease most significantly affected OCTT.

Conclusion

The OCTT models developed herein incorporate inter-subject variations and can contribute to providing more accurate predictions of drug pharmacokinetic profiles.

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Abbreviations

ADME:

absorption, distribution, metabolism and elimination

FDA:

Food and Drug Administration

GET:

gastric emptying time

GI:

gastrointestinal

LHBT:

lactulose hydrogen breath test

OCTT:

oro-cecal transit time

PK:

pharmacokinetics

SITT:

small intestine transit time

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Correspondence to Tohru Kokubo.

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Kokubo, T., Matsui, S. & Ishiguro, M. Meta-analysis of Oro-cecal Transit Time in Fasting Subjects. Pharm Res 30, 402–411 (2013). https://doi.org/10.1007/s11095-012-0882-6

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