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  • Bérénice Manczak,
  • Marie-Clémence Verdier,
  • Joseph Dewulf,
  • Florian Lemaitre,
  • Vincent Haufroid,
  • Philippe Hantson
Bérénice Manczak
Cliniques universitaires Saint-Luc
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Marie-Clémence Verdier
Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)-UMR_S 1085, Rennes
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Joseph Dewulf
Cliniques universitaires Saint-Luc
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Florian Lemaitre
Centre Hospitalier Universitaire de Rennes
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Vincent Haufroid
Université Catholique de Louvain
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Philippe Hantson
Cliniques St-Luc, Université catholique de Louvain

Corresponding Author:[email protected]

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A 53-year-old woman with a history of acute myeloid leukemia received a second allogenic hematopoietic stem cell transplant (HSCT) and was prescribed, among other medications, acyclovir and letermovir (480 mg daily oral dose) for prophylaxis of respectively herpes simplex and cytomegalovirus infection. The patient was admitted in the intensive care unit (ICU) for dyspnea and oliguria. Laboratory investigations revealed acute kidney injury, but also a severe and progressive lactic acidosis. Liver function tests were within normal range. The combination of lactic acidosis, hypoglycaemia and acylcarnitine profile in plasma suspected a mitochondrial toxicity. Letermovir therapy was interrupted and determination of plasma letermovir pharmacokinetics revealed a prolonged terminal half-life (40.7 h) that was not significantly influenced by continuous venovenous hemofiltration. Exploration for genetic polymorphisms revealed that the patient was SLCO1B1*5/*15 (c.521T>C homozygous carrier and c.388A>G heterozygous carrier) with a predicted non-functional OATP1B1 protein. The relationship between letermovir accumulation and development of lactic acidosis requires further observations.
14 Dec 2022Submitted to British Journal of Clinical Pharmacology
15 Dec 2022Submission Checks Completed
15 Dec 2022Assigned to Editor
15 Dec 2022Review(s) Completed, Editorial Evaluation Pending
15 Dec 2022Reviewer(s) Assigned
11 Jan 2023Editorial Decision: Revise Minor
23 Jan 20231st Revision Received
24 Jan 2023Assigned to Editor
24 Jan 2023Submission Checks Completed
24 Jan 2023Review(s) Completed, Editorial Evaluation Pending
24 Jan 2023Editorial Decision: Revise Minor
25 Jan 20232nd Revision Received
27 Jan 2023Assigned to Editor
27 Jan 2023Submission Checks Completed
27 Jan 2023Review(s) Completed, Editorial Evaluation Pending
31 Jan 2023Editorial Decision: Accept