Trevor N. Johnson

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BACKGROUND Prediction of the exposure of neonates, infants and children to xenobiotics is likely to be more successful using physiologically based pharmacokinetic models than simplistic allometric scaling, particularly in younger children. However, such models require comprehensive information on the ontogeny of anatomical, physiological and biochemical(More)
BACKGROUND AND OBJECTIVE Liver cirrhosis is characterized by a decrease in functional hepatocytes, lowered circulating levels of plasma proteins and alterations in blood flow due to the development of portacaval shunts. Depending on the interplay between these parameters and the characteristics of an administered drug, varying degrees of impaired systemic(More)
AIMS To investigate the effects of age and disease states on the expression and activity of intestinal CYP3A4 in a paediatric population. METHODS Duodenal biopsies and surgical sections were collected from 104 paediatric patients (age range 2 weeks to 17 years) and from 11 foetuses. An S9 fraction was prepared in each case. CYP3A4 expression was assessed(More)
A diversity of equations is available for the estimation of liver volume (LV), derived from studies in populations of ethnically homogeneous individuals and using a variety of methods of measurement. The aim of this study was to integrate all published pediatric data and to define a general equation for estimating LV from birth onward. Data were collated(More)
AIMS Pregnant women are usually not part of the traditional drug development programme. Pregnancy is associated with major biological and physiological changes that alter the pharmacokinetics (PK) of drugs. Prediction of the changes to drug exposure in this group of patients may help to prevent under- or overtreatment. We have used a pregnancy(More)
Most of the drugs on the market are originally developed for adults and dosage selection is based on an optimal balance between clinical efficacy and safety. The aphorism 'children are not small adults' not only holds true for the selection of suitable drugs and dosages for use in children but also their susceptibility to adverse drug reactions. Since(More)
AIMS AND OBJECTIVES (i) To describe an example of the development work required for building a 'pediatric physiologically based pharmacokinetic' (P-PBPK) model (Simcyp Pediatric ADME Simulator), (ii) to replicate pediatric clinical studies and undertake theoretical studies to show the potential applications of mechanistic PBPK in pediatric drug clinical(More)
The presence of cytochrome P450 enzymes in the small bowel results in the reduced bioavailability of several drugs. Recently, there has been much research on the interplay between these enzymes and transporter proteins such as P-glycoprotein. Intestinal drug metabolism not only has an effect on drug disposition but also may have a role in protecting the(More)
The magnitude of any metabolic drug-drug interactions (DDIs) depends on fractional importance of inhibited pathway which may not necessarily be the same in young children when compared to adults. The ontogeny pattern of cytochrome P450 (CYP) enzymes (CYPs 1A2, 2B6, 2C8, 2C9, 2C18/19, 2D6, 2E1, 3A4) and renal function were analyzed systematically. Bootstrap(More)