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Mechanistic Modeling of the Drug-Drug Interaction Between Efavirenz and Dolutegravir: Is This Interaction Clinically Relevant When Switching From Efavirenz to Dolutegravir During Pregnancy?
This study aimed at developing physiologically based pharmacokinetic models to simulate the switch from efavirenz to dolutegravir in the late second and third trimester. To this end, the drug-drug interaction between efavirenz and the uridine 5'-diphospho-glucuronosyltransferase 1A1 substrates dolutegravir and raltegravir was first simulated in nonpregnant subjects. After successful validation, the physiologically based pharmacokinetic models were translated to pregnancy and dolutegravir pharmacokinetics following efavirenz discontinuation were predicted. Modeling results indicated that, at the end of the second trimester,...
Source: The Journal of Clinical Pharmacology - June 15, 2023 Category: Drugs & Pharmacology Authors: Andr é Dallmann John van den Anker Homa K Ahmadzia Natella Rakhmanina Source Type: research

Congenital malformations and preeclampsia associated with integrase inhibitor use in pregnancy: A single-center analysis
ConclusionIn our cohort, first-trimester INSTI exposure was associated with increased rates of congenital anomalies and use of INSTI during pregnancy was associated with preeclampsia. These findings underscore the need for continued monitoring of the safety of INSTI in pregnancy. (Source: PLoS One)
Source: PLoS One - June 12, 2023 Category: Biomedical Science Authors: Christiana Smith Source Type: research

Management of Drug Interactions with Inducers: Onset and Disappearance of Induction on Cytochrome P450 3A4 and Uridine Diphosphate Glucuronosyltransferase 1A1 Substrates
ConclusionsOur simulations support the common practice of maintaining the adjusted dosage of a drug for another 2 weeks after stopping an inducer. Furthermore, our simulations suggest that an inducer should be administered for at least 14 days before conducting interaction studies to reach maximal induction. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - June 6, 2023 Category: Drugs & Pharmacology Source Type: research

Total, unbound, renal and hepatic clearances of raltegravir and the formation and elimination clearances of raltegravir glucuronide in pregnant women
This article is protected by copyright. All rights reserved.PMID:37260039 | DOI:10.1002/jcph.2287 (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - June 1, 2023 Category: Drugs & Pharmacology Authors: Fernanda de Lima Moreira Tiago Antunes Paz Patr ícia Pereira Dos Santos Melli Matheus de Lucca Thomaz Maria Paula Marques Adriana Rocha Geraldo Duarte Vera Lucia Lanchote Source Type: research

PRESTIGIO RING: "A 59-year-old HIV-1 positive, highly treatment-experienced woman failing darunavir/ ritonavir plus raltegravir"
New Microbiol. 2023 May;46(2):226-230.ABSTRACTManagement of heavily treatment experienced (HTE) people with HIV remains a challenge. Tailored antiretroviral therapy (ART) is needed in this fragile population who almost invariably harbor viral quasispecies with resistance-associated mutations (RAMs). The reference method for HIV genotypic resistance testing (GRT) has long been Sanger sequencing (SS), but next-generation sequencing (NGS), following recent progress in workflow and cost-effectiveness, is replacing SS because of higher sensitivity. From the PRESTIGIO Registry, we present a case of a 59-year-old HTE woman who fa...
Source: New Microbiologica - May 29, 2023 Category: Microbiology Authors: Laura Labate Bianca Bruzzone Vincenzo Spagnuolo Maurizio Zazzi Maria Mercedes Santoro Antonio Di Biagio Antonella Castagna Source Type: research