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25 results on '"Cox, Shareen"'

14. Pharmacokinetics and Pharmacodynamics of Mycophenolic Acid and Their Relation to Response to Therapy of Childhood-Onset Systemic Lupus Erythematosus

Author

Sagcal-Gironella, Anna Carmela P., primary, Fukuda, Tsuyoshi, additional, Wiers, Kristina, additional, Cox, Shareen, additional, Nelson, Shannen, additional, Dina, Blair, additional, Sherwin, Catherine M.T., additional, Klein-Gitelman, Marisa S., additional, Vinks, Alexander A., additional, and Brunner, Hermine I., additional

Published
2011
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21. UGT1A9, UGT2B7, and MRP2Genotypes Can Predict Mycophenolic Acid Pharmacokinetic Variability in Pediatric Kidney Transplant Recipients

Author

Fukuda, Tsuyoshi, Goebel, Jens, Cox, Shareen, Maseck, Denise, Zhang, Kejian, Sherbotie, Joseph R., Ellis, Eileen N., James, Laura P., Ward, Robert M., and Vinks, Alexander A.

Abstract

Mycophenolic acid (MPA) exposure in pediatric patients with kidney transplant receiving body surface area (BSA)–based dosing exhibits large variability. Several genetic variants in glucuronosyltransferases (UGTs) and of multidrug resistance–associated protein 2 (MRP2) have independently been suggested to predict MPA exposure in adult patients with varying results. Here, the combined contribution of these genetic variants to MPA pharmacokinetic variability was investigated in pediatric renal transplant recipients who were on mycophenolic mofetil maintenance therapy.

Published
2012
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22. Carbamazepine Plasma Concentration: Relationship to Cognitive Impairment

Author

O'Dougherty, Margaret, Wright, Francis S., Cox, Shareen, and Walson, Philip

Abstract

• Neuropsychological function was assessed before and after carbamazepine monotherapy in children with newly diagnosed complex partial epilepsy. Simultaneous video-electroencephalographic monitoring examined the influence of subclinical abnormal electrical discharges on performance. Total and unbound plasma carbamazepine concentrations were examined in relation to changes in performance at low (carbamazepine level, ≤32 μmol/L [≤7.5 mg/L]) and moderate (carbamazepine level, >34 μmol/L [>8.0 mg/L]) drug levels. The data suggest a mild beneficial effect of carbamazepine on speeded eye-hand coordination and, at low drug levels, more rapid processing of items in memory. Efficiency of learning new information and memory-scanning rate displayed a concentration-dependent relationship with carbamazepine level, with poor performance significantly associated with higher carbamazepine plasma concentrations. Carbamazepine free levels were equivalent to total levels in predicting cognitive side effects.

Published
1987
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23. Phenytoin AgeDoseConcentration Relationship in Children

Author

Suzuki, Yasuhiro, Mimaki, Takashi, Cox, Shareen, Koepke, John, and Hayes, John

Abstract

A list (n = 423) of phenytoin steady-state concentrations from children taking phenytoin alone or in combination with other drugs (n = 308) was obtained from our therapeutic drug monitoring database (1984–1990). Only 43 of concentrations were within the commonly accepted “therapeutic” or “reference” range (10–20 mg/L). Age-dose-concentration relationships showed that while occasional concentrations were above 20 mg/L, many patients receiving commonly recommended pediatric phenytoin doses (4–8 mg/ kg/day) achieved concentrations below the reference range, especially children under 3 years of age. Michaelis-Menten pharmacokinetic parameters, maximal elimination rate (Vmax) and Michaelis constant (Km), were evaluated for patients with at least two steady-state concentrations measured for two or more different daily doses. Comedication with other drugs had no effect on either Vmaxor Kmfor phenytoin. Vmaxappeared to decrease significantly with age, but there was no age relationship for Km.

Published
1994

25. Population pharmacokinetic-pharmacodynamic modelling of mycophenolic acid in paediatric renal transplant recipients in the early post-transplant period.

Author

Dong M, Fukuda T, Cox S, de Vries MT, Hooper DK, Goebel J, and Vinks AA

Subjects
Adolescent, Child, Child, Preschool, Dose-Response Relationship, Drug, Graft Rejection enzymology, Graft Rejection immunology, Graft Rejection prevention & control, Humans, Immunosuppressive Agents blood, Mycophenolic Acid blood, Predictive Value of Tests, Tissue Distribution, Young Adult, IMP Dehydrogenase antagonists & inhibitors, Immunosuppressive Agents pharmacokinetics, Immunosuppressive Agents pharmacology, Kidney Transplantation, Models, Biological, Mycophenolic Acid pharmacokinetics, Mycophenolic Acid pharmacology
Abstract

Aim: The purpose of this study was to develop a population pharmacokinetic and pharmacodynamic (PK-PD) model for mycophenolic acid (MPA) in paediatric renal transplant recipients in the early post-transplant period., Methods: A total of 214 MPA plasma concentrations-time data points from 24 patients were available for PK model development. In 17 out of a total of 24 patients, inosine monophosphate dehydrogenase (IMPDH) enzyme activity measurements (n = 97) in peripheral blood mononuclear cells were available for PK-PD modelling. The PK-PD model was developed using non-linear mixed effects modelling sequentially by 1) developing a population PK model and 2) incorporating IMPDH activity into a PK-PD model using post hoc Bayesian PK parameter estimates. Covariate analysis included patient demographics, co-medication and clinical laboratory data. Non-parametric bootstrapping and prediction-corrected visual predictive checks were performed to evaluate the final models., Results: A two compartment model with a transit compartment absorption best described MPA PK. A non-linear relationship between dose and MPA exposure was observed and was described by a power function in the model. The final population PK parameter estimates (and their 95% confidence intervals) were CL/F, 22 (14.8, 25.2) l h(-1) 70 kg(-1) ; Vc /F, 45.4 (29.6, 55.6) l; Vp /F, 411 (152.6, 1472.6)l; Q/F, 22.4 (16.0, 32.5) l h(-1) ; Ka , 2.5 (1.45, 4.93) h(-1) . Covariate analysis in the PK study identified body weight to be significantly correlated with CL/F. A simplified inhibitory Emax model adequately described the relationship between MPA concentration and IMPDH activity. The final population PK-PD parameter estimates (and their 95% confidence intervals) were: E0 , 3.45 (2.61, 4.56) nmol h(-1)  mg(-1) protein and EC50 , 1.73 (1.16, 3.01) mg l(-1) . Emax was fixed to 0. There were two African-American patients in our study cohorts and both had low IMPDH baseline activities (E0 ) compared with Caucasian patients (mean value 2.13 mg l(-1) vs. 3.86 mg l(-1) )., Conclusion: An integrated population PK-PD model of MPA has been developed in paediatric renal transplant recipients. The current model provides information that will facilitate future studies and may be implemented in a Bayesian algorithm to allow a PK-PD guided therapeutic drug monitoring strategy., (© 2014 The British Pharmacological Society.)

Published
2014
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