scholarly journals Integrated semi-physiological pharmacokinetic model for both sunitinib and its active metabolite SU12662

2015 ◽  
Vol 79 (5) ◽  
pp. 809-819 ◽  
Author(s):  
Huixin Yu ◽  
Neeltje Steeghs ◽  
Jacqueline S. L. Kloth ◽  
Djoeke de Wit ◽  
J. G. Coen van Hasselt ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Pharmacokinetic Model ◽  
Physiological Pharmacokinetic Model

Physiological pharmacokinetic model for ceftazidime disposition in the rat and its application to prediction of plasma concentrations in humans

1993 ◽  
Vol 1 (1) ◽  
pp. 3-11 ◽  
Author(s):  
Luis Granero ◽  
Jesús Chesa-Jiménez ◽  
Víctor Monserrat ◽  
Mercedes Almela ◽  
María-José Gimeno ◽  
...  
Keyword(s):  
Pharmacokinetic Model ◽  
Plasma Concentrations ◽  
Physiological Pharmacokinetic Model

scholarly journals A physiological pharmacokinetic model describing the disposition of lycopene in healthy men

2003 ◽  
Vol 44 (10) ◽  
pp. 1927-1939 ◽  
Author(s):  
Veda Diwadkar-Navsariwala ◽  
Janet A. Novotny ◽  
David M. Gustin ◽  
Jeffery A. Sosman ◽  
Keith A. Rodvold ◽  
...  
Keyword(s):  
Pharmacokinetic Model ◽  
Healthy Men ◽  
Physiological Pharmacokinetic Model

scholarly journals Development of a Population Pharmacokinetic Model for Parecoxib and Its Active Metabolite Valdecoxib after Parenteral Parecoxib Administration in Children

2012 ◽  
Vol 116 (5) ◽  
pp. 1124-1133 ◽  
Author(s):  
Bruce Hullett ◽  
Sam Salman ◽  
Sean J. O'Halloran ◽  
Deborah Peirce ◽  
Kylie Davies ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Pharmacokinetic Model ◽  
Inhibitory Concentration ◽  
Prediction Interval ◽  
Cyclooxygenase 2 ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Concentration Time

Background Parecoxib is a cyclooxygenase-2 selective inhibitor used in management of postoperative pain in adults. This study aimed to provide pediatric pharmacokinetic information for parecoxib and its active metabolite valdecoxib. Methods Thirty-eight children undergoing surgery received parecoxib (1 mg/kg IV to a maximum of 40 mg) at induction of anesthesia, and plasma samples were collected for drug measurement. Population pharmacokinetic parameters were estimated using nonlinear mixed effects modeling. Area under the valdecoxib concentration-time curve and time above cyclooxygenase-2 in vitro 50% inhibitory concentration for free valdecoxib were simulated. Results A three-compartment model best represented parecoxib disposition, whereas one compartment was adequate for valdecoxib. Age was linearly correlated with parecoxib clearance (5.0% increase/yr). There was a sigmoid relationship between age and both valdecoxib clearance and distribution volume. Time to 50% maturation was 87 weeks postmenstrual age for both. In simulations using allometric-based doses the 90% prediction interval of valdecoxib concentration-time curve in children 2-12.7 yr included the mean for adults given 40 mg parecoxib IV. Simulated free valdecoxib plasma concentration remained above the in vitro 50% inhibitory concentrations for more than 12 h. In children younger than 2 yr, a dose reduction is likely required due to ongoing metabolic maturation. Conclusions The final pharmacokinetic model gave a robust representation of parecoxib and valdecoxib disposition. Area under the valdecoxib concentration-time curve was similar to that in adults (40 mg), and simulated free valdecoxib concentration was above the cyclooxygenase-2 in vitro 50% inhibitory concentration for free valdecoxib for at least 12 h.

Adjusting Exposure Limits for Long and Short Exposure Periods Using A Physiological Pharmacokinetic Model

AIHAJ ◽  
1987 ◽  
Vol 48 (4) ◽  
pp. 335-343 ◽  
Author(s):  
MELVIN E. ANDERSEN ◽  
MICHAEL G. MacNAUGHTON ◽  
HARVEY J. CLEWELL III ◽  
DENNIS J. PAUSTENBACH
Keyword(s):  
Pharmacokinetic Model ◽  
Short Exposure ◽  
Exposure Limits ◽  
Physiological Pharmacokinetic Model

Physiological Pharmacokinetic Model of Hexachlorobenzene in the Rat

1989 ◽  
Vol 57 ◽  
pp. 139-147 ◽  
Author(s):  
R. A. Freeman ◽  
K. K. Rozman ◽  
A. G. E. Wilson
Keyword(s):  
Pharmacokinetic Model ◽  
Physiological Pharmacokinetic Model

scholarly journals Bayesian Parameter Estimates of Nelfinavir and Its Active Metabolite, Hydroxy-tert-Butylamide, in Infants Perinatally Infected with Human Immunodeficiency Virus Type 1

2005 ◽  
Vol 49 (2) ◽  
pp. 525-535 ◽  
Author(s):  
Salomé Payen ◽  
Albert Faye ◽  
Alexandra Compagnucci ◽  
Carlo Giaquinto ◽  
Diana Gibbs ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Body Weight ◽  
Human Immunodeficiency Virus Type ◽  
Active Metabolite ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
Immunodeficiency Virus

ABSTRACT The objective of the present study was to develop a population pharmacokinetic model for nelfinavir mesylate (NFV) and nelfinavir hydroxy-tert-butylamide (M8), the most abundant metabolite of NFV, in infants vertically infected with human immunodeficiency virus type 1 and participating in the Paediatric European Network for Treatment of AIDS 7 study. Plasma NFV concentrations were determined during repeated NFV administrations (two to three times a day). Eighteen infants younger that age 2 years participated in this study. The doses administered ranged from 71 to 203 mg/kg of body weight/day. Pharmacokinetic parameter estimates were obtained by a compartmental approach by using a kinetic model to simultaneously fit NFV and M8 (active metabolite) concentrations. M8 was shown to be formation rate limited and was characterized by first-order rate constants of formation and elimination. Body weight was found to be a more appropriate predictor than age of the changes in (i) the rate of metabolism, (ii) the elimination rate constant of NFV, and (iii) NFV clearance. Population parameters were computed to account for the relationship between the rate of metabolism and body weight. The estimated NFV and M8 elimination half-lives were 4.3 and 2.04 h, respectively. The estimated NFV clearance was 2.13 liters/h/kg. The M8 concentration-to-NFV concentration ratio was 0.64 ± 0.44. In conclusion, the population pharmacokinetic model describing the dispositions of NFV and M8 should facilitate the design of future studies to elucidate the relative contributions of the parent compound and M8 to the pharmacological and toxic effects of NFV therapy.

Development and Application of a Mechanistic Pharmacokinetic Model for Simvastatin and its Active Metabolite Simvastatin Acid Using an Integrated Population PBPK Approach

2014 ◽  
Vol 32 (6) ◽  
pp. 1864-1883 ◽  
Author(s):  
Nikolaos Tsamandouras ◽  
Gemma Dickinson ◽  
Yingying Guo ◽  
Stephen Hall ◽  
Amin Rostami-Hodjegan ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Pharmacokinetic Model ◽  
Simvastatin Acid
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