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Hydrocortisone (Cortef)

Corticosteroidprescriptionoral · predicted

Short-acting glucocorticoid for adrenal replacement and anti-inflammatory/immunosuppressive therapy. Bioavailability ~96%; short plasma half-life (1.2-2 hours) requires 2-3 daily doses. Biologic half-life ~8-12 hours due to genomic mechanisms. Cortisol replacement ~20 mg/day mimics physiologic production (~5.7-9.9 mg/m2/day). Minimal first-pass metabolism. Used for Addison's disease, adrenal insufficiency, inflammatory conditions.

Projected serum levels — 20 mg, twice daily

Hydrocortisone (Cortef)
Hydrocortisone (Cortef) modeled serum levels, 20 mg twice daily over 15 days Population-based pharmacokinetic estimate. Steady state reached after approximately 1 days. 0 5 10 15 20 Day 0 Day 4 Day 7 Day 11 Day 15 Time on a regular schedule ≈ steady state · day 1
Hydrocortisone (Cortef) modeled serum levels with a loading dose of 24.4 mg, then 20 mg twice daily The first dose is larger so levels approach steady state faster. 0 5 10 15 20 Day 0 Day 4 Day 7 Day 11 Day 15 Time on a regular schedule

Maintenance schedule: 20 mg twice daily (oral).

Loading schedule: 24.4 mg on day 1, then 20 mg twice daily — reaching therapeutic levels sooner.

Modeled steady state after ~1 days: peak ≈ 19.1 mg, trough ≈ 4.1 mg body load. Population-based estimate over 15 days for a 20 mg dose at a 70 kg reference body mass — the interactive app scales curves to your doses, timing, and body mass.

Key facts

Category
Corticosteroid
Route modeled
Oral
Model confidence
predicted
Half-life
1.7 h
Common dose
20 mg
Suggested maximum
300 mg/day
Reference dose range
10–300 mg (single dose)
Suggested cadence
twice daily
Validated against
20 mg oral — Cmax 0.45 mg/L at 1 h

Documented interactions

  • contraindicated
    Efavirenz (Sustiva) + Hydrocortisone (Cortef) CYP induction

    Efavirenz (Sustiva) inducer of CYP3A4 predicted to change Hydrocortisone (Cortef) AUC by ~0.19x

  • contraindicated
    Rifampin + Hydrocortisone (Cortef) CYP induction

    Rifampin inducer of CYP3A4 predicted to change Hydrocortisone (Cortef) AUC by ~0.19x

  • danger
    Carbamazepine (Tegretol) + Hydrocortisone (Cortef) CYP induction

    Carbamazepine (Tegretol) inducer of CYP3A4 predicted to change Hydrocortisone (Cortef) AUC by ~0.29x

  • danger
    Clarithromycin (Biaxin) + Hydrocortisone (Cortef) CYP inhibition

    Clarithromycin (Biaxin) mechanism_based of CYP3A4 predicted to change Hydrocortisone (Cortef) AUC by ~2.17x

  • danger
    Diltiazem + Hydrocortisone (Cortef) CYP inhibition

    Diltiazem mechanism_based of CYP3A4 predicted to change Hydrocortisone (Cortef) AUC by ~2.17x

  • danger
    Grapefruit (whole fruit) + Hydrocortisone (Cortef) CYP inhibition

    Grapefruit (whole fruit) mechanism_based of CYP3A4 predicted to change Hydrocortisone (Cortef) AUC by ~2.17x

Serum checks 73 modeled interaction pairings for hydrocortisone (cortef) across your whole stack — absorption conflicts, enzyme inhibition, and nutrient depletion included.

Research behind this entry

  1. Variability in hydrocortisone plasma and saliva pharmacokinetics following intravenous and oral administration to patients with adrenal insufficiency Peacey SR et al. · Journal of Clinical Endocrinology & Metabolism, 2008 DOI

    Study in adrenal insufficiency showing high inter-individual PK variability (up to 10-fold), bioavailability ~96%, Tmax 1.2±0.4 hours, and short elimination half-life requires individualized dosing.

  2. Replacement therapy of oral hydrocortisone in adrenal insufficiency: the influence of gastrointestinal factors Bleicken B et al. · Journal of Clinical Endocrinology & Metabolism, 2008 DOI

    Investigation of GI factors affecting hydrocortisone absorption; demonstrates bioavailability minimally affected by meal timing or gastric pH, but variability remains high requiring dose adjustments.

  3. Pharmacokinetics of oral hydrocortisone: Results and implications from a randomized controlled trial Johannsson G et al. · Metabolism: Clinical and Experimental, 2017 DOI

    RCT showing standard immediate-release hydrocortisone produces suprathysiologic peaks and troughs; modified-release formulations better approximate physiologic cortisol rhythm.

3 published studies referenced in the app, each with a plain-language summary.