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

Bioavailability Studies of Acetaminophen and Nitrofurantoin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97190/1/j.1552-4604.1974.tb02312.x.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

Blood ethanol concentrations during and following constant‐rate intravenous infusion of alcohol

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/117025/1/cpt1976192213.pd

Association of endocrine active environmental compounds with body mass index and weight loss following bariatric surgery

IntroductionThe objective of this study was to study associations of a wide range of halogenated biphenyls, dibenzo‐p‐dioxins, dibenzofurans, and diphenylethers with body mass index (BMI) and evaluate changes in their concentration following bariatric surgery.MethodsSubcutaneous fat, visceral fat, and liver tissue samples were collected from 106 patients undergoing Roux‐en‐Y gastric bypass surgery for weight loss or patients who were undergoing abdominal surgery for non‐bariatric reasons. We measured concentrations of an extensive panel of chlorinated and brominated biphenyls, dioxins, and furans, and brominated diphenylethers in the samples. We conducted linear regression to examine associations with BMI, adjusting for age and gender. Changes in concentration for indicator chemicals were evaluated in samples collected following bariatric surgery in a small sub‐population.ResultsAfter adjustments for age and gender and correction for multiple testing, seven ortho‐chlorinated biphenyls, one non‐ortho‐chlorinated biphenyl, four PCDD/F’s and one ortho‐brominated biphenyl were associated with BMI. The strongest associations between BMI and lipid‐adjusted concentrations were seen with PCB‐105 in subcutaneous fat (beta=16.838 P‐val=1.45E‐06) PCB‐126 in visceral fat (beta=15.067 P‐val=7.72E‐06) and PCB‐118 (beta=14.101 P‐val=2.66E‐05) in liver. The concentrations of sum PCBs, chlorinated toxic equivalent quantity (TEQ's) and brominated compounds increased significantly with weight loss in subcutaneous fat in a group of ten individuals resampled up to five years after bariatric surgery and substantial weight loss.ConclusionWe show that selected polychlorinated biphenyls PCBs and structurally related polychlorinated dibenzo‐p‐dioxins dibenzofurans (PCDD/Fs) were associated with BMI. Concentrations of these lipophilic compounds in subcutaneous fat increased following bariatric surgery