Acute Porphyria Drugs

Acute Porphyria Drug Database

J05AF01 - Zidovudine
Propably not porphyrinogenic
PNP
Important Information
Side effects like nausea may potentially be porphyrinogenic through reduction in carbohydrate intake.
Side effects
A very common side effect of zidovudine is nausea. Other common side effects are vomiting, diarrhoea and abdominal pains. These side effects can be confused with an acute attack and may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Rationale
Zidovudine is not suspected to be a mechanism-based inhibitor or an inducer of CYP enzymes.
Chemical description
Pyrimidine nucleoside, a synthetic thymidine analogue
Therapeutic characteristics
Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) indicated for the anti-retroviral combination treatment of HIV-1. It is also used to prevent mother-to-child virus transmission in pregnancy. Elimination half-life is 1 hour. It is administered orally.
Metabolism and pharmakokinetics
Zidovudine is mainly metabolized by glucuronide conjugation to an inactive metabolite (SPC), but several hepatic CYP enzymes are also suspected to be involved in the metabolism (Eagling 1994, Pan-Zhou 1998). Zidovudine has been found to reduce ALAS-2 activity in bone marrow cells of drug-treated animals, and depleted heme level was observed in erythroid cells and not in hepatic cells (Lutton 1990). Zidovudine is not reported to be a mechanism-based inhibitor or an inducer of CYP enzymes (Hisaka 2010, Isoherranen 2009, Pelkonen 2008), and no drug-drug interactions involving CYP enzymes with zidovudine as a perpetrator has been reported in the literature (SPC, interaktionsdatabasen.dk).
Published experience
There is one case report of uneventful use in a patient with HCP (Herrero 1990)

References

  1. Scientific articles
  2. Eagling VA, Howe JL, et al. The metabolism of zidovudine by human liver microsomes in vitro: formation of 3´-amino-3´-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76. #1803
  3. Herrero C, Bassas S, et al. Acquired immunodeficiency syndrome in a patient affected by hereditary coproporphyria: safety of zidovudine treatment. Arch Dermatol. 1990 Jan;126(1):122-3. #1804
  4. Hisaka A, Ohno Y, et al. Prediction of pharmacokinetic drug-drug interaction caused by changes in cytochrome P450 activity using in vivo information. Pharmacol Ther. 2010 Feb;125(2):230-48. #1138
  5. Isoherranen N, Hachad H, et al. Qualitative analysis of the role of metabolites in inhibitory drug-drug interactions: literature evaluation based on the metabolism and transport drug interaction database. Chem Res Toxicol. 2009 Feb;22(2):294-8. #1005
  6. Lutton JD, Mathew A, et al. Role of heme metabolism in AZT-induced bone marrow toxicity. Am J Hematol. 1990 Sep;35(1):1-5. PMID 2389764. #4542
  7. Pan-Zhou XR, Cretton-Scott E, et al. Role of human liver P450s and cytochrome b5 in the reductive metabolism of 3´-azido-3´-deoxythymidine (AZT) to 3´-amino-3´-deoxythymidine. Biochem Pharmacol. 1998 Mar 15;55(6):757-66. PMID 9586947. #4541
  8. Pelkonen O, Turpeinen M, et al. Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol. 2008 Oct;82(10):667-715. PMID 18618097. #4347
  9. Drug interaction databases
  10. Interaktionsdatabasen. Zidovudine. #1805
  11. Summary of Product Characteristics
  12. The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). (Retrovir). #1808
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