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Development of a physiologically based pharmacokinetic model of actinomycin D in children with cancer.

Walsh C, Bonner JJ, Johnson TN, Neuhoff S, Ghazaly EA, Gribben JG, Boddy AV, Veal GJ - Br J Clin Pharmacol (2016)

Bottom Line: Simulated values for actinomycin D AUC0-26h and clearance in infants aged 0-12 months ranged from 104 to 115 ng h ml(-1) and 3.5-3.8 l h(-1) , respectively.However, additional independent data from neonates and infants is needed for further validation.Physiological differences between paediatric cancer patients and healthy children also need to be further characterized and incorporated into PBPK models.

View Article: PubMed Central - PubMed

Affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.

No MeSH data available.


Related in: MedlinePlus

Graph showing the rate of movement of Act D across the MDCKII‐MDR1 monolayer at various concentrations
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bcp12878-fig-0002: Graph showing the rate of movement of Act D across the MDCKII‐MDR1 monolayer at various concentrations

Mentions: The Transwell™ assay to characterize the enzyme kinetics of transport of Act D by ABCB1 (MDR1) determined the maximum rate of flux (Jmax) to be 1142 μM min−1/106 cells, with a Michaelis–Menten constant (Km) of 20 μM. Figure 2 shows the rate of efflux vs. Act D concentration curve which appears to have reached a plateau by 100 μM.


Development of a physiologically based pharmacokinetic model of actinomycin D in children with cancer.

Walsh C, Bonner JJ, Johnson TN, Neuhoff S, Ghazaly EA, Gribben JG, Boddy AV, Veal GJ - Br J Clin Pharmacol (2016)

Graph showing the rate of movement of Act D across the MDCKII‐MDR1 monolayer at various concentrations
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834588&req=5

bcp12878-fig-0002: Graph showing the rate of movement of Act D across the MDCKII‐MDR1 monolayer at various concentrations
Mentions: The Transwell™ assay to characterize the enzyme kinetics of transport of Act D by ABCB1 (MDR1) determined the maximum rate of flux (Jmax) to be 1142 μM min−1/106 cells, with a Michaelis–Menten constant (Km) of 20 μM. Figure 2 shows the rate of efflux vs. Act D concentration curve which appears to have reached a plateau by 100 μM.

Bottom Line: Simulated values for actinomycin D AUC0-26h and clearance in infants aged 0-12 months ranged from 104 to 115 ng h ml(-1) and 3.5-3.8 l h(-1) , respectively.However, additional independent data from neonates and infants is needed for further validation.Physiological differences between paediatric cancer patients and healthy children also need to be further characterized and incorporated into PBPK models.

View Article: PubMed Central - PubMed

Affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.

No MeSH data available.


Related in: MedlinePlus