drug accumulation ratio

In pharmacokinetics, the drug accumulation ratio (R_ac) is the ratio of accumulation of a drug under steady state conditions (i.e., after repeated administration) as compared to a single dose. The higher the value, the more the drug accumulates in the body. An R_ac of 1 means no accumulation.

Studies

The accumulation ratio of a specific drug in humans is determined by clinical studies. According to a 2013 analysis, such studies are typically done with 10 to 20 subjects who are given one single dose followed by a washout phase of seven days (median), and then seven to 14 repeated doses to reach steady state conditions. Blood samples are drawn 11 times (median) per subject to determine the blood concentration of the studied drug.

Calculation

File:Drug accumulation ratio.svg

There are various competing calculation methods for the drug accumulation ratio, yielding somewhat different results. A commonly used formula defines R_ac as the ratio of the area under the curve (AUC) during a single dosing interval under steady state conditions to the AUC during a dosing interval after one single dose:{{cite journal|doi=10.2174/13892002113149990002|title=Systematic Evaluation of Dose Accumulation Studies in Clinical Pharmacokinetics|year=2013|last1=Li|first1=Lujin|last2=Li|first2=Xianxing|last3=Xu|first3=Ling|last4=Sheng|first4=Yucheng|last5=Huang|first5=Jihan|last6=Zheng|first6=Qingshan|journal=Current Drug Metabolism|volume=14|issue=5|pages=605–615|pmid=23701162}}

: $R_{ac} = \frac {\operatorname{AUC}(\tau,ss)} {\operatorname{AUC}(\tau,1)}$

where $\tau$ is the dosing interval, ss means steady state and 1 stands for a single-dose application.

Another definition sets R_ac to the ratio of the average drug concentration during one day under steady state conditions to the concentration after a single dose.{{cite journal|doi=10.1002/j.1552-4604.1997.tb04271.x|title=A Simplified Account of Drug Accumulation and Steady-State Dose Equivalences|year=1997|last1=Swartz|first1=Conrad M.|journal=The Journal of Clinical Pharmacology|volume=37|issue=10|pages=962–970|pmid=9505988}}

Examples

class="wikitable" ! Drug !! Trade name !! R_ac !! Reference
Dabrafenib	Tafinlar	0.73	{{cite web\|url=https://www.ema.europa.eu/en/documents/product-information/tafinlar-epar-product-information_en.pdf\|title=Tafinlar: EPAR – Product Information\|publisher=European Medicines Agency\|date=1 February 2021}}
Rosuvastatin	Crestor	1.37 in hemodialysis patients	{{cite journal\|pmid=23494963\|year=2013\|last1=Birmingham\|first1=B. K.\|last2=Swan\|first2=S. K.\|last3=Puchalski\|first3=T.\|last4=Mitchell\|first4=P.\|last5=Azumaya\|first5=C.\|last6=Zalikowski\|first6=J.\|last7=Wang\|first7=Y.\|title=Pharmacokinetic and pharmacodynamic profile of rosuvastatin in patients with end-stage renal disease on chronic haemodialysis\|journal=Clinical Drug Investigation\|volume=33\|issue=4\|pages=233–241\|doi=10.1007/s40261-013-0071-3}}
Lisinopril	Prinivil and others	1.38	{{cite journal\|pmid=2547465\|year=1989\|last1=Beermann\|first1=B.\|last2=Till\|first2=A. E.\|last3=Gomez\|first3=H. J.\|last4=Hichens\|first4=M.\|last5=Bolognese\|first5=J. A.\|last6=Junggren\|first6=I.\|title=Pharmacokinetics of lisinopril (IV/PO) in healthy volunteers\|journal=Biopharmaceutics & Drug Disposition\|volume=10\|issue=4\|pages=397–409\|doi=10.1002/bdd.2510100407}}
Ivacaftor	Kalydeco	2.2–2.9	{{cite web\|url=https://www.ema.europa.eu/en/documents/product-information/kalydeco-epar-product-information_en.pdf\|title=Kalydeco: EPAR – Product Information\|publisher=European Medicines Agency\|date=12 May 2021}}
Trametinib	Mekinist	6.0 at 2 mg once daily	{{cite web\|url=https://www.ema.europa.eu/en/documents/product-information/mekinist-epar-product-information_en.pdf\|title=Mekinist: EPAR – Product Information\|publisher=European Medicines Agency\|date=26 February 2021}}

References

Category:Pharmacokinetic metrics