Hi

Dexamethasone is not "long half-life" drug. Generally long half life in synthetic drugs means t1/2kel longer than 24 h. Dexamethasone half-life is circa 4 h so its relatively short, see for example tablet formulation t1/2kel

https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211379Orig1s000ClinPharmR.pdf

Definition of "Long half-life drugs" by FDA

" long elimination half-life drug (>24 hrs) "

Reference:

https://www.fda.gov/files/drugs/published/Bioequivalence-Studies-With-Pharmacokinetic-Endpoints-for-Drugs-Submitted-Under-an-Abbreviated-New-Drug-Application.pdf

Best source to check PK data of approved drugs is FDA homepage see link below:

https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm

To get fast acces for label of any drug you can use google and keywords like this:

FDA label dexamethasone pdf

Good source of basic and advanced information about PK and multiple dosing and relationship between PK parameters and dosing is boomer.org

Examples:

Advanced:

Chapter 14 Multiple IV Bolus Dose Administration

https://www.boomer.org/c/p4/c14/c1404.php

Basic:

https://www.boomer.org/c/p4/#topics

Best regards

Tomasz

Thank you for the correction on the t1/2 life and the resources! What I was going for was the biological t1/2 for dexamethasone is long (>36hrs) as it is long acting glucocorticoid. Thus, why is it dosed Q6h for intracranial pressure? does the metabolites have different effect?

Hi,

Hope good explanation is here:

" Several preparations of glucocorticoids are available, each with varying efficacy. (...) Equivalent glucocorticoid doses can be calculated for these various preparations. 5 mg of prednisone is equivalent in its glucocorticoid effects to 5 mg of prednisolone, 4 mg of methylprednisolone, 4 mg of triamcinolone, 0.75 mg of dexamethasone, 0.60 mg of betamethasone, 20 mg of cortisol and 25 mg of cortisone. "

and your question about metabolites:

"The glucocorticoid and mineralocorticoid effects of each available preparation varies, with cortisol and cortisone having almost 1 to 1 glucocorticoid and mineralocorticoid effects while all others with almost no mineralocorticoid effects."

https://www.ncbi.nlm.nih.gov/books/NBK531462/

affinity of glucocorticoids for target receptors is different and have huge impact on potency and efficacy.

https://academic.oup.com/jcem/article-abstract/54/2/332/2676702?redirectedFrom=fulltext

so current dosing schemes take it into account, some other differences are dependent on bioavailability and many other factors see document below.

As you see label below dosing regiment is corrected according to glucocorticoid efficacy - 36h (see below is i line with this approach)

0.28-0.57 mg/kg (70 kg BW) Recomended dose 20-40 mg every 24 h

0.20-0.40 mg/kg (70 kg BW) Recomended dose 20-40 mg every 24 h

(https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211379s000lbl.pdf)

Finaly

" Since complications of treatment with corticosteroids are dependent on the size of the dose and the duration of treatment, a risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used. "

" In cerebral edema, Dexamethasone Sodium Phosphate injection, USP is generally administered initially in a dosage of 10 mg intravenously followed by 4 mg every six hours intramuscularly until the symptoms of cerebral edema subside. Response is usually noted within 12 to 24 hours and dosage may be reduced after two to four days and gradually discontinued over a period of five to seven days. "

Dexamethasone suppression tests. Tests for Cushing's syndrome

"For greater accuracy, give 0.5 mg of DECADRON orally every 6 hours for 48 hours. (...) Test to distinguish Cushing's syndrome due to pituitary ACTH excess from Cushing's syndrome due to other causes. Give 2.0 mg of DECADRON orally every 6 hours for 48 hours. "

https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/11664slr062_decadron_lbl.pdf

See below differences between dosage and treatement methods.

https://www.pdr.net/drug-summary/Dexamethasone-Sodium-Phosphate-Injection--USP-4-mg-mL-dexamethasone-sodium-phosphate-3062

Check out this article- Article The Operational Multiple Dosing Half-life: A Key to Defining...

Its all about the Pharmacokinetics of drugs and due to the need for a special concentration that should maintain in plasma for a drug in therapeutic window to be effective.

Check this out:

Article Pharmacokinetics made easy 11 Designing dose regimens