Hello
in the use of drugs of which the dosing involves a loading dose then a maintenance dose, how to best calculate the time interval between the loading dose and the first maintenance dose following? And are there any special considerations for specific drugs?
Hi,
It depends on the dose ratio D (loading dose/maintenance dose).
D is also known as the accumulation index, D= 1/1-e-ke.t where ke is the elimination constant (Ke=ln2/T1/2), and t the dosing interval
For a dose ratio of 2, dosing interval equals the drug biological half life (T1/2)
For a dose ratio >2, dosing interval is < drug half life
For a dose ratio drug half life
Best regards,
normally, it takes 3-4 x t1/2 to reach steady-state (~90% SS) using a fixed dosing frequency. with a loading dose, it shortens the time taking to reach SS.
The dosing interval determination can be determined by using simulation if the PK profiles behaves as multiexponential terms. Usually, we need to know a target exposure for efficacy to achieve or toxicity to avoid (therapeutic window). For different drug class, the exposure target could be Cmax, Cmin or AUC. For antibiotic agents, we usually classify then into concentration dependent drugs or time dependent drugs. For the former, we need to optimize the concentration (less frequent dosing); for the latter we need to optimize the time i.e. maintaining drug concentration above certain threshold for enough long time (more frequent dosing).
Most of the drugs following first order kinetics reach steady state plasma concentration after 4 to 5 doses. Based on its t 1/2 and elimination kinetics (Cmax, Tmax, AUC) etc the dose interval will be fixed. More the t1/2 less the frequency.
Hi Ayman
Please find attached the below link which you may find useful for addressing your issue
https://www.nps.org.au/australian-prescriber/articles/pharmacokinetics-made-easy-11-designing-dose-regimens
If I understand the question well it is to pay attention to the elimination half of T / 2 that is different for certain drugs! Therapeutic concentration will be rapidly reached by medications with T1 / 2 over time, and vice versa will require more individual doses in T / 2 shorter intervals. It is also important to take into account the long half-life of T1 / 2 elimination, it is necessary to measure drug concentrations in the blood (determination of blood concentrations in HPLC) To avoid accumulation and drug toxicity!
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