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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

Systemic concentration of Act D vs. time for 100 simulated patients less than one year of age given 1.25 mg m−2 IV mean, 5th and 95th (0–<3 months, 3–<6 months, 6–12 months)
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bcp12878-fig-0005: Systemic concentration of Act D vs. time for 100 simulated patients less than one year of age given 1.25 mg m−2 IV mean, 5th and 95th (0–<3 months, 3–<6 months, 6–12 months)

Mentions: For the younger age ranges (example profile, Figure 3B), all AUC predictions were within two‐fold of the observed values, with simulated data from six of the eight age/dose ranges falling within 15% of the observed data (Table 4). The level of variability as compared to the observed values ranged from 1‐ to 1.8‐fold. Simulations for very young children (0–<3, 3–<6 and 6–12 months old) showed comparable PK profile shape to the older children, with mean AUC0‐26h values of 104.07, 109.99 and 115.42 ng h ml−1 and clearance values of 3.5, 3.6 and 3.8 l h−1 determined, respectively (Figure 5).


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)

Systemic concentration of Act D vs. time for 100 simulated patients less than one year of age given 1.25 mg m−2 IV mean, 5th and 95th (0–<3 months, 3–<6 months, 6–12 months)
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

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

bcp12878-fig-0005: Systemic concentration of Act D vs. time for 100 simulated patients less than one year of age given 1.25 mg m−2 IV mean, 5th and 95th (0–<3 months, 3–<6 months, 6–12 months)
Mentions: For the younger age ranges (example profile, Figure 3B), all AUC predictions were within two‐fold of the observed values, with simulated data from six of the eight age/dose ranges falling within 15% of the observed data (Table 4). The level of variability as compared to the observed values ranged from 1‐ to 1.8‐fold. Simulations for very young children (0–<3, 3–<6 and 6–12 months old) showed comparable PK profile shape to the older children, with mean AUC0‐26h values of 104.07, 109.99 and 115.42 ng h ml−1 and clearance values of 3.5, 3.6 and 3.8 l h−1 determined, respectively (Figure 5).

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