Bioavailability of imipramine tablets relative to a stable isotope-labeled internal standard: Increasing the power of bioavailability tests

  title={Bioavailability of imipramine tablets relative to a stable isotope-labeled internal standard: Increasing the power of bioavailability tests},
  author={H A Heck and S. E. Jun. Buttrill and Norman W. Flynn and Robert L. Dyer and Michael Anbar and Thomas Cairns and Shrikant V. Dighe and Bernard E. Cabana},
  journal={Journal of Pharmacokinetics and Biopharmaceutics},
A new methodology for comparative bioavailability testing is described in which each drug formulation is compared with a stable isotope-labeled variant of the drug that is consumed orally in solution at the same time the tested formulation is ingested. The methodology is used to determine the comparative bioavailabilities of two commercially available brands of imipramine hydrochloride. The power of the new methodology to detect differences between drug formulations, when, in fact, such… 

Superiority of stable isotope techniques in the assessment of the bioavailability of drugs undergoing extensive first pass elimination

Using this technique the bioavailability of verapamil tablets (Isoptin® 80) relative to a stable labelled solution of verAPamil was found to be 108.1%, with a 95% confidence interval between 89.1 and 127.1%.

The stable isotope method for determining absolute bioavailability

  • A. Atkinson
  • Biology
    Translational and clinical pharmacology
  • 2017
The bioavailability of a drug is usually assessed in healthy subjects. However, it is reasonable to expect that significant alterations in bioavailability may occur in actual patients with different

The use of isotopes in the determination of absolute bioavailability of drugs in humans

This work has shown that isotopic labelling not only allows for the accurate and efficient determination of absolute bioavailability, but can also provide information on first-pass effects and other pharmacokinetic parameters.

Re-introduction of a Novel Approach to the Use of Stable Isotopes in Pharmacokinetic Studies

Utilization of a stable isotope approach can markedly improve the efficiency and accuracy of bioavailability and bioequivalence studies particularly for highly variable drugs in formulations that are qualitatively and quantitatively the same and for studies designed for QbD investigations.

Evaluation of the utility of a proposed method for correcting for intrasubject variability in metabolic clearance in the bioavailability assessment of theophylline

A method is proposed for compensating for changes in metabolic clearance from the reference intravenous to the test oral treatments and it is shown that this method can be appropriately made by a stable isotope coadministration technique.

Drug absorption and bioavailability

  • A. Atkinson
  • Biology
    Atkinson's Principles of Clinical Pharmacology
  • 2022

Applications of stable isotopes in clinical pharmacology.

The application of stable isotope technology in the assessment of drug pharmacology to determine the pharmacokinetic profile or mode of action of a drug substance and in relation to patient-specific drug treatment is reviewed.

The assessment of bioavailability in the presence of nonlinear elimination

The tracer method appears to be a robust means of assessing, in man, oral bioavailability in the presence of Michaelis-Menten type elimination for drugs characterized by the general properties of the physiological model employed and with half-lives in excess of approximately 40 min.

Implications of intraindividual variability in bioavailability studies of furosemide

Intrasubject variation in bioavailability (rate and extent) and disposition of furosemide 40 mg was investigated using a repeated, randomized, double-blind cross-over study in 8 healthy subjects and bioequivalence was demonstrated for the two generic tablets.

A Non-Invasive, Low-Cost Study Design to Determine the Release Profile of Colon Drug Delivery Systems: A Feasibility Study

Breath and urine 13C and 15N data describe the release-profile and local bioavailability of a colon delivery device that allows non-invasive bioavailability studies for evaluation of colon-specific drug delivery systems without radioactive exposure and with increased power and strongly reduced costs.



Determination of imipramine in plasma by high pressure liquid chromatography and field ionization mass spectrometry: increased sensitivity in comparison with gas chromatography mass spectrometry.

A quantitative method is reported for the determination of imipramine in plasma samples in the low nanogram and subnanogram range with sensitivity and precision approximately an order of magnitude greater than are offered by gas chromatography mass spectrometry with selected ion monitoring using deuterated or other types of internal standards.

Use of confidence intervals in analysis of comparative bioavailability trials.

  • W. Westlake
  • Medicine
    Journal of pharmaceutical sciences
  • 1972

Introduction to Statistical Analysis, McGraw-Hill

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Statistics for Scientists and Engineers.

By reading, you can know the knowledge and things more, not only about what you get from people to people. Book will be more trusted. As this statistics for scientists and engineers, it will really

Bioavailability Policies and Guidelines

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