Prediction of the Clearance of Eleven Drugs and Associated Variability in Neonates, Infants and Children
The in silico prediction of pharmacokinetic behaviour in paediatric patients is not intended to replace clinical studies, however, it provides a valuable aid to decision-making with regard to first-time dosing in children and study design.
'In silico' simulations to assess the 'in vivo' consequences of 'in vitro' metabolic drug-drug interactions.
A Semi-Mechanistic Model to Predict the Effects of Liver Cirrhosis on Drug Clearance
- T. Johnson, K. Boussery, K. Rowland-Yeo, G. Tucker, A. Rostami-Hodjegan
- MedicineClinical Pharmacokinetics
- 1 March 2010
Predictions of the effects of liver cirrhosis on drug clearance are of potential value in the design of clinical studies during drug development and, clinically, in the assessment of likely dosage adjustment.
Changes in liver volume from birth to adulthood: A meta‐analysis
A more general model to predict LV in pediatric populations and young adults is developed and its precision and accuracy was found to be superior to those of 10/11 published adult models.
Anatomical, Physiological and Metabolic Changes with Gestational Age during Normal Pregnancy
- K. Abduljalil, P. Furness, T. Johnson, A. Rostami-Hodjegan, H. Soltani
- MedicineClinical Pharmacokinetics
- 1 June 2012
The collected data presented in this paper provide a potentially useful singular resource for key parameters needed for PBPK modelling in pregnancy, which facilitates the risk assessment of environmental chemicals and therapeutic drug dose adjustments in the pregnant population.
Modeling and predicting drug pharmacokinetics in patients with renal impairment
- K. Rowland Yeo, M. Aarabi, M. Jamei, A. Rostami-Hodjegan
- Medicine, BiologyExpert Review of Clinical Pharmacology
- 1 March 2011
The application of a systems biology approach to simulate drug disposition in subjects with renal impairment is discussed, which may help in the selection of a safe and effective dosage regimen.
Physiologically Based Pharmacokinetics Joined With In Vitro–In Vivo Extrapolation of ADME: A Marriage Under the Arch of Systems Pharmacology
- A. Rostami-Hodjegan
- BiologyClinical pharmacology and therapy
- 1 July 2012
PBPK–IVIVE linked models have repeatedly shown their value in guiding decisions when predicting the effects of intrinsic and extrinsic factors on PK of drugs, and a review of the achievements and shortcomings of the models might suggest better strategies in extending the success of PBPK-IVIVE to pharmacodynamics (PD) and drug safety.
A PBPK Model to Predict Disposition of CYP3A-Metabolized Drugs in Pregnant Women: Verification and Discerning the Site of CYP3A Induction
- A. Ke, S. Nallani, P. Zhao, A. Rostami-Hodjegan, J. Unadkat
- Biology, MedicineCPT: Pharmacometrics & Systems Pharmacology
- 1 September 2012
The PBPK model is a useful tool to evaluate different dosing regimens during T3 for drugs cleared primarily via CYP3A metabolism, and a sensitivity analysis suggested that CYP 3A induction in T3 is most likely hepatic and not intestinal.
A pregnancy physiologically based pharmacokinetic (p-PBPK) model for disposition of drugs metabolized by CYP1A2, CYP2D6 and CYP3A4.
- L. Gaohua, K. Abduljalil, M. Jamei, T. Johnson, A. Rostami-Hodjegan
- Medicine, BiologyBritish Journal of Clinical Pharmacology
- 1 November 2012
In the absence of clinical data, the in silico prediction of PK behaviour during pregnancy can provide a valuable aid to dose adjustment in pregnant women.
Resurgence in the use of physiologically based pharmacokinetic models in pediatric clinical pharmacology: parallel shift in incorporating the knowledge of biological elements and increased…
An example of the development work required for building a ‘pediatric physiologically based pharmacokinetic’ (P‐PBPK) model (Simcyp Pediatric ADME Simulator) is described and the potential applications of mechanistic PBPK in pediatric drug clinical investigation and practice are shown.