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A personal Evidencio account is free , with no strings attached! Join us and help create clarity, transparency, and efficiency in the creation, validation, and use of medical prediction models. If the time to achieve steady state is longer than desired, an initial loading dose of a drug can be administered to reach the desired blood concentration quickly. Note: The loading dose is based on the volume of distribution and the maintenance dose is based on the half-life of the drug administered.
This model is provided for educational, training and information purposes. It must not be used to support medical decision making, or to provide medical or diagnostic services. Read our full disclaimer. Use your email to log in. Please enter a password. Enter an authorization code. A password has to be at least 8 characters. A password cannot be longer then 64 characters. Choose a password with at least one capital letter.
Didn't receive the email yet? Please check your spam folder, or resend the email. Terms of use. The next morning, you replace the candies so your office mate will never be the wiser. The input rate is the same as the elimination rate.
For most drugs, the time to reach steady state is four to five half-lives if the drug is given at regular intervals—no matter the number of doses, the dose size, or the dosing interval. A half-life is how long it takes for half of the drug to be eliminated from the body.
If a single dose is given every half-life, half of the first dose will be cleared from the body before the next dose. So, after the second dose, there will be 1.
Half of that is eliminated and then the next dose is given, meaning there are now 1. At dose 5 after five half-lives , there will be close to two doses in the body, which means one entire dose is eliminated each dosing interval. If we continue dosing at the same frequency, the amount we dose will be eliminated during each dosing interval. As a result, drug concentrations in the body remain constant steady. Another way to think about steady state:.
But a very simple way to remember it is that the average C ss is the total exposure AUC over one dosing interval divided by the duration of the dosing interval. For a drug with a short half-life, steady state is achieved pretty quickly.
If you have a drug with a long half-life and a patient who needs to achieve a therapeutic effect fast—for example, a critical care patient who needs antibiotics—how can you get that effect without having to wait days or weeks? Phenytoin has dose-dependent kinetics of elimination.
Phenytoin is hydroxylated in the liver by an enzyme system that is saturable at high plasma levels , hence small incremental doses may increase the half-life and produce very substantial increases in serum levels , when these are in the upper range.
Urinary excretion of phenytoin and its metabolites occurs partly with glomerular filtration but, more importantly, by tubular secretion. The plasma half-life in man after oral administration of phenytoin averages 22 hours, with a range of 7 to 42 hours.
When serum level determinations are necessary, they should be obtained at least half-lives after treatment initiation, dosage change, or addition or subtraction of another drug to the regimen so that equilibrium or steady-state will have been achieved.
Trough levels provide information about clinically effective serum level range and confirm patient compliance and are obtained just prior to the patient's next scheduled dose. Peak levels indicate an individual's threshold for emergence of dose-related side effects and are obtained at the time of expected peak concentration. There may be wide inter-patient variability in phenytoin serum levels with equivalent dosages.
Patients with unusually low levels may be non-compliant or hyper-metabolizers of phenytoin. Unusually high levels result from liver disease, congenital enzyme deficiency or drug interactions which result in metabolic interference. Aspirin acetylsalicylic acid is rapidly hydrolyzed primarily in the liver to salicylic acid, which is conjugated with glycine forming salicyluric acid and glucuronic acid and excreted largely in the urine. The plasma half-life for aspirin is approximately 15 minutes ; but the half-life for salicylate lengthens as the dose increases :.
Salicylates are excreted mainly by the kidney. Brunton LL Editor. Reference: wikipedia.
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