D11AX22 - Ivermectin |
Propably not porphyrinogenic |
PNP |
Side effects
Ivermectin has no physiological actions or side effects of relevance to acute porphyria.
Rationale
Ivermectin is not an inhibitor or an inducer of any major CYP enzymes, and therefore no pharmacokinetic porphyrinogenic effects are suspected.
Chemical description
Macrocyclic lactone, a semisynthetic derivative of avermectins produced by Streptomyces avermitilis.
Therapeutic characteristics
Ivermectin is indicated for the topical treatment of inflammatory lesions of rosacea in adult patients.
It is applied once daily for up to four months.
Metabolism and pharmakokinetics
Topically administered ivermectin is absorbed systemically, but the Cmax is much lower. Cmax measured at the plateau (reached after two weeks of administration topically) is about one tenth of the Cmax reached after oral administration of ivermectin (SPC, Canga 2008)
Taken orally, ivermectin is a substrate of P-glycoprotein and of CYP 3A4 (Zeng 1998, Kiki-Mvouaka 2010), and to a minor degree CYP 2D6 and CYP 2E1 (Prescribing information, Merck & Co).
The findings of in vitro studies using human liver microsomes suggest that clinically relevant concentrations of ivermectin do not significantly inhibit the metabolizing activities of CYP3A4, CYP2D6, CYP2C9, CYP1A2, and CYP2E1 (Prescribing information, Merck & Co).
Ivermectin did not induce the expression of CYP 1A2, 2B6, 2C9 or 3A4 in cultured human hepatocytes (SPC).
References
- Scientific articles
- Canga A G, Prieto AMS et al. The pharmacokinetics and interactions of ivermectin in humans--a mini-review. AAPS J. 2008;10(1):42-6. PMID 18446504. #4711
- Kiki-Mvouaka S, Menez C et al. Role of P-glycoprotein in the disposition of macrocyclic lactones: A comparison between ivermectin, eprinomectin, and moxidectin in mice. Drug Metab Dispos. 2010 Apr;38(4):573-80. PMID 20089736. #4712
- Zeng Z, Andrew NW et al. Identification of cytochrome P4503A4 as the major enzyme responsible for the metabolism of ivermectin by human liver microsomes. Xenobiotica. #3241
- Drug reference publications
- Micromedex 2.0 (electronic version). Ivermectin. (Drugdex System). (11.02.2014). #2857
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Soolantra. #2859
- Other sources
- Prescribing information. STROMECTOL(R) oral tablets, ivermectin oral tablets. Merck & Co, Inc, Whitehouse Station, NJ, 2009. #2858
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