Monograph
C01CA17 - Midodrine |
Propably not porphyrinogenic |
PNP |
Rationale
Midodrine is a relatively low-dose oral prodrug giving rise to metabolite with affinity to CYP2D6, CYP1A2 and CYP2C19. Available data speak against major CYP induction or irreversible CYP inhibition of relevance.
Therapeutic characteristics
Midodrine is an α-agonist prodrug of desglymidodrine indicated for the treatment of symptomatic orthostatic hypotension.
A common side effect that can be confused with an acute porphyria attack is abdominal pain.
Dosing is 2,5-10 mg 3 times/day (maximum: 40 mg/day).
Metabolism and pharmacokinetics
Miodrine undergoes enzymatic hydrolysis in the systemic circulation to the active metabolite desglymidodrine. Desglymidodrine was shown in human liver microsomes to be metabolised by CYP2D6, CYP1A2 and to a minor degree by CYP2C19 (Akimoto 2004).
A small in vivo study indicated that midodrine might have increased bioavailability and decreased clearance of promethazine (Platts 2006) and is therefore listed as an inhibitor of CYP2D6 (Flockhart 2007, Polasek 2011). However, it is not listed as clinically relevant (Flockhart 2007).
The protein binding of midodrine is minimal and half-life elimination is 25 minutes. The half-life elimination of desglymidodrine is 3-4 hours.
IPNet drug reports
Uneventful use reported in 1 patient with acute porphyria.
References
| # | Citation details | PMID |
|---|---|---|
| * | Scientific articles | |
| 1. | The in vitro metabolism of desglymidodrine, an active metabolite of prodrug midodrine by human liver microsomes.
Akimoto M, Iida I, et al. Eur J Drug Metab Pharmacokinet. 2004 Jul-Sep;29(3):179-86. |
15537169 |
| 2. | Akathisia with combined use of midodrine and promethazine.
Platts SH, Shi SJ, Meck JV. JAMA. 2006 May 3;295(17):2000-1. |
16670408 |
| 3. | Perpetrators of pharmacokinetic drug-drug interactions arising from altered cytochrome P450 activity: a criteria-based assessment.
Polasek TM, Lin FP, et al. Br J Clin Pharmacol. 2011 May;71(5):727-36. |
21223357 |
| * | Drug reference publications | |
| 4. | Up to date. midodrine
|
|
| * | Drug interaction databases | |
| 5. | Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007).
Flockhart DA. |
|
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