A Mathematical Model of the Glucose-tolerance test

Ackerman, Eugene; Rosevear, John W.; McGuckin, Warren F.

doi:10.1088/0031-9155/9/2/307

Cited by 151 publications

(72 citation statements)

References 3 publications

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“…1 In fact, we find that for all the four turnover models I-IV -whether nonlinear or linear -the peak time T max converges to the same positive value as the drug dose becomes small:…”

Section: Property Bmentioning

confidence: 73%

A Dynamical Systems Analysis of the Indirect Response Model with Special Emphasis on Time to Peak Response

Peletier

Gabrielsson

Haag³

2005

J Pharmacokinet Pharmacodyn

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In this paper we present a mathematical analysis of the four classical indirect response models. We focus on characteristics such as the evolution of the response R(t) with time t, the time of maximal/minimal response T max and the area between the response and the baseline AU C R , and the way these quantities depend on the drug dose, the dynamic parameters such as E max and EC 50 and the ratio of the fractional turnover rate k out to the elimination rate constant k of drug in plasma. We find that depending on the model and on the drug mechanism function, T max may increase, decrease, decrease and then increase, or stay the same, as the drug dose is increased. This has important implications for using the shift in T max as a diagnostic tool in the selection of an appropriate model.

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“…1 In fact, we find that for all the four turnover models I-IV -whether nonlinear or linear -the peak time T max converges to the same positive value as the drug dose becomes small:…”

Section: Property Bmentioning

confidence: 73%

A Dynamical Systems Analysis of the Indirect Response Model with Special Emphasis on Time to Peak Response

Peletier

Gabrielsson

Haag³

2005

J Pharmacokinet Pharmacodyn

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“…The protein concentration was determined by nephelometry (33). Ideal values should be 0.7-1.3 Klett units/mg indicating that the binding affinity of the antibody had not been affected (34).…”

Section: Methodsmentioning

confidence: 99%

Site-specific Conjugation on Serine → Cysteine Variant Monoclonal Antibodies

Stimmel¹,

Merrill²,

Kuyper³

et al. 2000

Journal of Biological Chemistry

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We have engineered a cysteine residue at position 442 (EU/OU numbering) in the third constant domain (C H 3) of the heavy chain of several IgGs with different specificities, isoforms, and variants with the intent to introduce a site for chemical conjugation. The variants were expressed in NS0 mouse myeloma cells, where monomeric IgG is the major form and formation of aggregate was minimal. Monomeric IgG contained no free thiol; however, it was discovered that the engineered thiols were reversibly blocked and could be reduced under controlled conditions. Following reduction, reactive thiol was conjugated with a cysteine-specific bifunctional chelator, bromoacetyl-TMT to a humanized 323/A3 IgG4 variant. Conjugation had no significant effect on antibody affinity. To prove that the conjugation was site-specific, an antibody-TMT conjugate was labeled with lutetium-177 and subjected to peptide mapping followed by sequence analysis. Glu-C digestion demonstrated that 91% of the label was recovered in the COOH-terminal peptide fragment containing the engineered cysteine.

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“…With various modifications, this model has been used for assessing glucose metabolism in various states of glucose intolerance, during the IVGTT [24][25][26] and also the oral glucose tolerance test (OGTT). [27][28][29] However, this first model turned out too simple to be an adequate representation of the complex glucose-insulin system. Bergman and Cobelli have thus proposed the minimal model with the remote insulin compartment added.…”

Section: Whole-body Glucose Regulation Modelmentioning

confidence: 99%