Defining the Importance of Age-Related Changes in Drug Clearance to Optimizing Aminoglycoside Dosing Regimens for Adult Patients with Cystic Fibrosis

2021 ◽  
Author(s):  
Roxane Rohani ◽  
Brian Hoff ◽  
Manu Jain ◽  
Alexander Philbrick ◽  
Sara Salama ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Drug Clearance ◽  
Adult Patients ◽  
Age Related ◽  
Dosing Regimens ◽  
Age Related Changes

scholarly journals Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Sílvia M. Illamola ◽  
Hoa Q. Huynh ◽  
Xiaoxi Liu ◽  
Zubin N. Bhakta ◽  
Catherine M. Sherwin ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Population Pharmacokinetics ◽  
Drug Disposition ◽  
Adult Patients ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Concentration Data ◽  
First Order ◽  
Dosing Regimens ◽  
Pulmonary Exacerbations

ABSTRACTPractitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy. This study was aimed to establish the population pharmacokinetics of amikacin in adults with cystic fibrosis. We used serum concentration data obtained during routine therapeutic drug monitoring and explored the influence of patient covariates on drug disposition. We performed a retrospective chart review to collect the amikacin dosing regimens, serum amikacin concentrations, blood sampling times, and patient characteristics for adults with cystic fibrosis admitted for treatment of acute pulmonary exacerbations. Amikacin concentrations were retrospectively collected for 49 adults with cystic fibrosis, and 192 serum concentrations were available for analysis. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling with the first-order conditional estimation method. A two-compartment model with first-order elimination best described amikacin pharmacokinetics. Creatinine clearance and weight were identified as significant covariates for clearance and the volume of distribution, respectively, in the final model. Residual variability was modeled using a proportional error model. Typical estimates for clearance, central and peripheral volumes of distribution, and intercompartmental clearance were 3.06 liters/h, 14.4 liters, 17.1 liters, and 0.925 liters/h, respectively. The pharmacokinetics of amikacin in individuals with cystic fibrosis seems to differ from those in individuals without cystic fibrosis. However, further investigations are needed to confirm these results and, thus, the need for variations in amikacin dosing. Future pharmacodynamic studies will potentially establish the optimal amikacin dosing regimens for the treatment of acute pulmonary exacerbations in adult patients with CF.

P12-20 Age-related changes in motor unit number estimates in adult patients with Charcot-Marie-Tooth type 1A

2010 ◽  
Vol 121 ◽  
pp. S176
Author(s):  
J.P. van Dijk ◽  
C. Verhamme ◽  
I.N. van Schaik ◽  
H.J. Schelhaas ◽  
E. Mans ◽  
...  
Keyword(s):  
Motor Unit ◽  
Adult Patients ◽  
Charcot Marie Tooth ◽  
Age Related ◽  
Tooth Type ◽  
Age Related Changes

Drug metabolism and ageing

2005 ◽  
Vol 11 (2) ◽  
pp. 51-56 ◽  
Author(s):  
Hilary Wynne
Keyword(s):  
Blood Flow ◽  
Older People ◽  
Liver Blood Flow ◽  
Drug Distribution ◽  
Drug Clearance ◽  
Cytochrome P450 Enzymes ◽  
Liver Size ◽  
Age Related ◽  
Co Morbidity ◽  
Age Related Changes

Older people are major consumers of drugs and because of this, as well as co-morbidity and age-related changes in pharmacokinetics and pharmacodynamics, are at risk of associated adverse drug reactions. While age does not alter drug absorption in a clinically significant way, and age-related changes in volume of drug distribution and protein binding are not of concern in chronic therapy, reduction in hepatic drug clearance is clinically important. Liver blood flow falls by about 35% between young adulthood and old age, and liver size by about 24–35% over the same period. First-pass metabolism of oral drugs avidly cleared by the liver and clearance of capacity-limited hepatically metabolized drugs fall in parallel with the fall in liver size, and clearance of drugs with a high hepatic extraction ratio falls in parallel with the fall in hepatic blood flow. In normal ageing, in general, activity of the cytochrome P450 enzymes is preserved, although a decline in frail older people has been noted, as well as in association with liver disease, cancer, trauma, sepsis, critical illness and renal failure. As the contribution of age, co-morbidity and concurrent drug therapy to altered drug clearance is impossible to predict in an individual older patient, it is wise to start any drug at a low dose and increase this slowly, monitoring carefully for beneficial and adverse effects.

Age-related changes in motor unit number estimates in adult patients with Charcot-Marie-Tooth type 1A

2010 ◽  
Vol 17 (8) ◽  
pp. 1098-1104 ◽  
Author(s):  
J. P. Van Dijk ◽  
C. Verhamme ◽  
I. N. Van Schaik ◽  
H. J. Schelhaas ◽  
E. Mans ◽  
...  
Keyword(s):  
Motor Unit ◽  
Adult Patients ◽  
Charcot Marie Tooth ◽  
Age Related ◽  
Tooth Type ◽  
Age Related Changes

Age-related changes of the 3′APOB-VNTR genotype pool in ageing cohorts

1998 ◽  
Vol 62 (2) ◽  
pp. 115-122 ◽  
Author(s):  
G. De BENEDICTIS ◽  
L. CAROTENUTO ◽  
G. CARRIERI ◽  
M. De LUCA ◽  
E. FALCONE ◽  
...  
Keyword(s):  
Age Related ◽  
Age Related Changes

Age-Related Changes in Flexible Listening: Studies on Meta-Audition and the False Hearing Effect

2012 ◽  
Author(s):  
Chad S. Rogers ◽  
Larry L. Jacoby ◽  
Mitchell S. Sommers ◽  
Arthur Wingfield
Keyword(s):  
Age Related ◽  
Listening Studies ◽  
Age Related Changes
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