Quantitative pooling of Michaelis-Menten equations in models with parallel metabolite formation paths

Pooling of Michaelis-Menten equations for models having parallel paths for formation of two or more metabolites is discussed. A theory which explains phenomena exhibited by pooled nonlinear pharmacokinetic systems and equations relating pooled Michaelis-Menten constants (V p , K p ) to microscopic constants (V i , K i ) are presented. The suitability of this type of pooling for use in pharmacokinetic modeling is also discussed. Use of pooling concepts in the design of clinical studies is demonstrated .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45042/1/10928_2005_Article_BF01061505.pd

Importance of the use of the appropriate pharmacokinetic model to analyze in vivo enzyme constants

Throughout the literature, enzyme constants have been derived by utilizing in vivo data and indirectly assuming that these data were described by the one-compartment open model. However, many drugs are probably best described by a two-compartment open model with Michaelis-Menten elimination kinetics. Simulated data, which obey the two-compartment open model with Michaelis-Menten elimination, and which illustrate some of the interesting properties of such models, are presented. Treatment of two-compartment data by one-compartment analysis is shown to result in a serious distortion of enzyme parameters (V m , K m ). For data which obey the two-compartment open model, estimation of the Michaelis-Menten constant (K m ) and the maximum velocity (V m ) by one-compartment analysis cannot be theoretically justified and therefore should be avoided .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45043/1/10928_2005_Article_BF01061506.pd

The theophylline‐enoxacin interaction: I. Effect of enoxacin dose size on theophylline disposition

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110004/1/cptclpt1988197.pd

Hepatic Abnormalities Associated with Aluminum Loading in Piglets

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141476/1/jpen0293.pd

Pharmacokinetics of orally administered acetaminophen in man

Average and individual sets of plasma concentration-time data for acetaminophen following two oral treatments were simultaneously fitted to the integrated equation describing the two-compartment open model with first-order absorption and lag time. The nonlinear least-squares program NONLIN and an IBM 360/67 digital computer were employed to estimate nine parameters (k A , k B , C A 0 , C B 0 , k 12 , k 21 , k el , and ). When the mean plasma concentrations were weighted according to the inverse of their variances, the parameter estimates more accurately reflected those for individual subjects in the disposition portion of the model. Depending on the relative magnitudes of the disposition rate constants (k 12 , k 21 , and k el ), the one-compartment open model can be used to predict equilibrium-state plasma levels even though the drug is really “two compartment.” Equations are presented which show when the one-compartment approximation is justified. Equations are also presented for calculation of loading doses for multiple dose regimens of any drug obeying the two-compartment open model and the equations are applied to acetaminophen .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45044/1/10928_2005_Article_BF01071309.pd

The theophylline‐enoxacin interaction: II. Changes in the disposition of theophylline and its metabolites during intermittent administration of enoxacin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109958/1/cptclpt1989160.pd

Atomic force microscopy study of human amylin (20-29) fibrils

Here we present atomic force microscopy images of the fibrils formed by human amylin(20-29). This peptide is a fragment of the polypeptide amylin, the major proteinaceous component of amyloid deposits found in cases of type-II diabetes mellitus. Our results demonstrate that the amylin(20-29) peptide fragment forms amyloid-like fibrils that display polymorphic structures. Twisting along the axis of fibrils was often observed in fibrils aged for 6 hours but disappeared in mature fibrils aged for longer time periods

Inspiring and transforming the pre-service teacher through authentic classroom preparation

In this chapter, a course design was examined that sought to bridge the university experience of PSTs with the rich and complex reality of classroom life through a focus on authenticity. By augmenting concepts with richly authentic materials and introducing classroom encounters through microteaching with simulated misbehaviour, PSTs were brought close to the reality of the classroom. Carefully selected streamable, unscripted video footage of actual classrooms enabled the analysis of key sequenced strategies. Each analysed strategywas supported by conceptual accounts from lecture materials and readings. These strategies were then practised through microteaching with role-play scenarios where PSTs re-enacted authentic school student behaviours, including challenging misbehaviours. Concept, strategy and modelling came together in this course to bring the reality of the classroom as near as possible. The effectiveness of the design was examined through in-depth semi-structured interviews of course participants’ post-teaching placements. Results showed a substantial positive self-assessed transfer in course learning into the school classroom—the primary goal of the course design. In addition to competence, a reduction in anxiety and stress due to a sense of preparedness was commented upon.Robert Matthew