Dosing rate

Dosing rate refers to the rate at which drug is administered, in mg/hour, mg/day, or equivalent. The choice of dosing rate is what determines the steady state concentration of a drug when given in a repeated dosing regimen. The target plasma concentration range for a drug is generally similar for most patients, since a similar degree of occupation of protein targets is generally required across a patient population. However, inter-individual variability in body weight and composition, age, hepatic enzyme levels, renal function etc. mean that different dosing rates would be required in different individuals to achieve similar steady state concentrations.

In practice, the therapeutic windows for most drugs are sufficiently wide that a similar dosing rate can be used in most patients, and even though the steady state concentrations will thus differ between patients, they will still lie within the therapeutic window. Further, drug formularies will provide recommended dosing rates, as well as recommended dose size(s) and interval(s) that will achieve the recommended rate. For example, a dosing rate of 240 mg/day could be given as a single 240 mg tablet, or as one 120 mg tablet every 12 hours, or as one 80 mg tablet every 8 hours, or as one 10 mg tablet every hour, etc. The dosing rate is identical in each case. What would differ in these scenarios is the variation between peak and trough concentrations, with variation (expressed as peak:trough ratio) being smaller when more small doses are administered at shorter time intervals. As such, if it is necessary to minimise fluctuations in plasma concentrations, you may need to reduce the size of each dose as well as the time interval between doses.

This process is a balancing act between optimal dosing parameters and patient compliance, as it is unlikely that patients will be willing to subject themselves to a dosing regimen that involves taking a tablet at very short time intervals for a prolonged period of time.

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An ABC of PK/PD Copyright © 2023 by Dr. Andrew Holt is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, except where otherwise noted.

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