ArticleClinical drug investigation2015
CYP3A4 polymorphism and lopinavir toxicity in an HIV-infected pregnant woman.
Article in Clinical drug investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- A comprehensive review of adverse events to drugs used in COVID-19 patients: Recent clinical evidence.European journal of clinical investigation · 2022Review
- Predictive association ofPharmacogenomics · 2021Review
- COVID-19: Therapeutics and Their Toxicities.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2020Review
- Individualized Protease Inhibitor Monotherapy: The Role of Pharmacokinetics and Pharmacogenetics in an Aged and Heavily Treated HIV-Infected Patient.Clinical drug investigation · 2019Article
- HIV protease inhibitors: a review of molecular selectivity and toxicity.HIV/AIDS (Auckland, N.Z.) · 2015Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytochrome P450 (CYP) 3A4 has been considered to be the most important enzyme system for metabolism of lopinavir/ritonavir (LPV/r), a widely used HIV protease inhibitor (PI) recommended during pregnancy. Herein we present a clinical case of a pregnant HIV-infected woman who was taking standard doses of LPV/r, 400/100 mg twice daily. The trough plasma concentrations for LPV were fourfold above that recommended for PI-pretreated patients and toxicity associated with LPV/r and PI regimens was observed. These high concentrations continued after delivery in spite of a dosage reduction. The pharmacogenetic analysis revealed a genetic polymorphism in the CYP3A4 gene that encodes a non-functional protein. The pharmacokinetic study could indicate the occurrence of a phenomenon of non-linear pharmacokinetics which would justify why dosage reduction after pregnancy did not proportionally affect the patient's degree of exposure to the drug. In addition, an increment in CYP3A activity during pregnancy could explain lower LPV/r exposure during this period compared to postpartum, despite the impaired activity of CYP3A4 caused by the polymorphism.
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Registered trials
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