Human Organ/Tissue Growth Algorithms that Include Obese Individuals and Black/White Population Organ Weight Similarities from Autopsy Data

Abstract

Physiologically based pharmacokinetic (PBPK) models need the correct organ/tissue weights to match various total body weights in order to be applied to children and the obese individual. Baseline data from Reference Man for the growth of human organs (adrenals, brain, heart, kidneys, liver, lungs, pancreas, spleen, thymus, and thyroid) were augmented with autopsy data to extend the describing polynomials to include the morbidly obese individual (up to 250 kg). Additional literature data similarly extends the growth curves for blood volume, muscle, skin, and adipose tissue. Collectively these polynomials were used to calculate blood/organ/tissue weights for males and females from birth to 250 kg, which can be directly used to help parameterize PBPK models. In contrast to other black/white anthropomorphic measurements, the data demonstrated no observable or statistical difference in weights for any organ/tissue between individuals identified as black or white in the autopsy reports.

In Vitro Age-Dependent Enzymatic Metabolism of Chlorpyrifos and Chlorpyrifos-Oxon in Human Hepatic Microsomes and Chlorpyrifos-Oxon in Plasma

“…However, other physiological changes may contribute to overall age-dependent pharmacokinetics. For example, age-dependent changes in liver volume (Young et al, 2009) will affect the overall metabolism rates of CPF and CPF-oxon (Fig. 7).…”

Less-invasive MR indices of clinically evident esophageal variceal bleeding in biliary atresia patients

“…35 The differences in the volume indexrelated ratios could partially relate to the differences in body weight between the Group A and Group B patients in our series. Since previous studies proposed that visceral organ weights increase with the total body weight in human neonates to adults, 36 we divided the SLPR and SVIPR by the body height and body weight, respectively, to obtain corrected ratios with sensitivity 100% for corrected SLPR. The SLPR per body height may be a good screening criterion irrespective of patient's age.…”

Derivation of human Biomonitoring Guidance Values for chlorpyrifos using a physiologically based pharmacokinetic and pharmacodynamic model of cholinesterase inhibition

“…The model has been primarily parameterized and validated using human data from in vitro and in vivo studies, and by a lesser extent by fitting the model to human exposure data. Data on human physiology is based on the growth models described by Luecke et al (2007) and Young et al (2009). CPF specific metabolism was measured in vitro and describes the detoxification to TCPy and bioactivation to CPF-oxon in the liver.…”