The importance of modeling interoccasion variability in population pharmacokinetic analyses

1993 ◽  
Vol 21 (6) ◽  
pp. 735-750 ◽  
Author(s):  
M. O. Karlsson ◽  
L. B. Sheiner
Keyword(s):  
Population Pharmacokinetic ◽  
Interoccasion Variability

scholarly journals Population Pharmacokinetics of Lamivudine in Human Immunodeficiency Virus-Exposed and -Infected Infants

2007 ◽  
Vol 51 (12) ◽  
pp. 4297-4302 ◽  
Author(s):  
Adriana H. Tremoulet ◽  
Edmund V. Capparelli ◽  
Parul Patel ◽  
Edward P. Acosta ◽  
Katherine Luzuriaga ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Individual Subject ◽  
Final Model ◽  
Interoccasion Variability ◽  
Immunodeficiency Virus ◽  
Hiv Exposed ◽  
The Individual

ABSTRACT This study aimed to determine lamivudine disposition in infants and to construct an appropriate dose adjustment for age, given the widespread use of lamivudine for both the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) and the treatment of HIV-infected infants. Using a pooled-population approach, the pharmacokinetics of lamivudine in HIV-exposed or -infected infants from four Pediatric AIDS Clinical Trials Group studies were assessed. Ninety-nine infants provided 559 plasma samples for measurement of lamivudine concentrations. All infants received combination antiretroviral therapy including lamivudine dosed at 2 mg/kg of body weight every 12 h (q12h) for the first 4 to 6 weeks of life and at 4 mg/kg q12h thereafter. Lamivudine's apparent clearance was 0.25 liter/h/kg at birth, doubling by 28 days. In the final model, age and weight were the only significant covariates for lamivudine clearance. While lamivudine is predominantly renally eliminated, the serum creatinine level was not an independent covariate in the final model, possibly because it was confounded by age. Inclusion of interoccasion variability for bioavailability improved the individual subject clearance prediction over the age range studies. Simulations based on the final model predicted that by the age of 4 weeks, 90% of infant lamivudine concentrations with the standard 2 mg/kg dose of lamivudine fell below the adult median concentration. This population pharmacokinetic analysis affirms that adjusting the dose of lamivudine from 2 mg/kg to 4 mg/kg q12 h at the age of 4 weeks for infants with normal maturation of renal function will provide optimal lamivudine exposure, potentially contributing to more successful therapy.

Methodological Approaches to Evaluate Fetal Drug Exposure

2019 ◽  
Vol 25 (5) ◽  
pp. 496-504 ◽  
Author(s):  
Naïm Bouazza ◽  
Frantz Foissac ◽  
Déborah Hirt ◽  
Saïk Urien ◽  
Sihem Benaboud ◽  
...  
Keyword(s):  
Cord Blood ◽  
Drug Exposure ◽  
Placental Transfer ◽  
Ex Vivo ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Pbpk Models ◽  
Drug Concentrations ◽  
Fetal Drug Exposure

Background: Drug prescriptions are usual during pregnancy, however, women and their fetuses still remain an orphan population with regard to drugs efficacy and safety. Most xenobiotics diffuse through the placenta and some of them can alter fetus development resulting in structural abnormalities, growth or functional deficiencies. Methods: To summarize the different methodologies developed towards the prediction of fetal drug exposure. Results: Neonatal cord blood concentration is the most specific measurement of the transplacental drug transfer at the end of pregnancy. Using the cord blood and mother drug concentrations altogether, drug exchanges between the mother and fetus can be modeled and quantified via a population pharmacokinetic analysis. Thereafter, it is possible to estimate the fetus exposure and the fetus-to-mother exposure ratio. However, the prediction of placental transfer before any administration to pregnant women is desirable. Animal studies remain difficult to interpret due to structural and functional inter-species placenta differences. The ex-vivo perfusion of the human placental cotyledon is the method of reference to study the human placental transfer of drugs because it is thought to mimic the functional placental tissue. However, extrapolation of data to in vivo situation remains difficult. Some research groups have extensively worked on physiologically based models (PBPK) to predict fetal drug exposure and showed very encouraging results. Conclusion: PBPK models appeared to be a very promising tool in order to predict fetal drug exposure in-silico. However, these models mainly picture the end of pregnancy and knowledge regarding both, development of the placental permeability and transporters is strongly needed.

scholarly journals Population Pharmacokinetic Model for Intravenous ASN100 in Healthy Subjects

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S529-S529
Author(s):  
Scott A Van Wart ◽  
Christopher Stevens ◽  
Zoltan Magyarics ◽  
Steven A Luperchio ◽  
Paul G Ambrose
Keyword(s):  
Healthy Subjects ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic

Population Pharmacokinetic Modeling of Etoposide Free Concentrations in Solid Tumor

2016 ◽  
Vol 33 (7) ◽  
pp. 1657-1670 ◽  
Author(s):  
Maiara Cássia Pigatto ◽  
Bibiana Verlindo de Araujo ◽  
Bruna Gaelzer Silva Torres ◽  
Stephan Schmidt ◽  
Paolo Magni ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Pharmacokinetic Modeling ◽  
Population Pharmacokinetic ◽  
Population Pharmacokinetic Modeling

scholarly journals Population pharmacokinetic modeling of molibresib and its active metabolites in patients with solid tumors: a semi‐mechanistic autoinduction model

2021 ◽  
Author(s):  
Anu Shilpa Krishnatry ◽  
Alexander Voelkner ◽  
Arindam Dhar ◽  
Marita Prohn ◽  
Geraldine Ferron‐Brady
Keyword(s):  
Solid Tumors ◽  
Pharmacokinetic Modeling ◽  
Population Pharmacokinetic ◽  
Active Metabolites ◽  
Population Pharmacokinetic Modeling
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