CYP3A4 Polymorphism and Lopinavir Toxicity in an HIV-Infected Pregnant Woman
| Autor: | María Paz Valverde Merino, Alicia Iglesias Gómez, Salvador Cabrera Figueroa, Alfonso Domínguez-Gil Hurlé, Elena López Aspiroz |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
CYP3A HIV Infections Pharmacology Polymorphism Single Nucleotide Lopinavir Pharmacokinetics Pregnancy Cytochrome P-450 CYP3A Humans Medicine HIV Protease Inhibitor Pharmacology (medical) Pregnancy Complications Infectious CYP3A4 business.industry HIV Protease Inhibitors General Medicine medicine.disease Toxicity Female Ritonavir business medicine.drug |
| Zdroj: | Clinical Drug Investigation. 35:61-66 |
| ISSN: | 1179-1918 1173-2563 |
| DOI: | 10.1007/s40261-014-0245-7 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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