Pharmacokinetics-pharmacodynamics of sertraline as an antifungal in HIV-infected Ugandans with cryptococcal meningitis

Alhadab, Ali A.; Rhein, Joshua; Tugume, Lillian; Musubire, Abdu K; Williams, Darlisha A; Abassi, Mahsa; Nicol, Melanie R.; Meya, David B.; Boulware, David R.; Brundage, Richard C.; Team, Astro-Cm

doi:10.1007/s10928-019-09657-0

Cited by 5 publications

(3 citation statements)

References 48 publications

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“…The study by Alhadab et al, (2019) investigated the role of sertraline as an adjunct in the treatment of HIV-associated cryptococcal meningitis in Ugandan patients receiving AmB, antiretrovirals (ART) and FLZ. A one-compartment PK model with first order absorption and elimination by exploratory sigmoidal E max -model was used.…”

Section: Fluconazolementioning

confidence: 99%

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The role of modeling and simulation to improve the treatment of fungal infections caused by Cryptococcus : A literature review

Staudt,

Olivo,

Alves

et al. 2024

Braz. J. Pharm. Sci.

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The treatment of fungal infections presents problems in relation to toxicity, pharmacokinetic properties, and undesirable side effects among other factors. An alternative to clarify some of these problems is the use of mathematical modeling and simulation of the pharmacokinetics and pharmacodynamics data of antifungals, in order to seek greater support in decision making regarding the treatment of Cryptococcus infection. Here, we describe the results of

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Section: Fluconazolementioning

confidence: 99%

“…The use of antiretrovirals was included as a covariate in CL/F. SER increased the exposure of FLZ in the brain which increased the fungal clearance of CSF (Alhadab et al, 2019).…”

Section: Fluconazolementioning

confidence: 99%

The role of modeling and simulation to improve the treatment of fungal infections caused by Cryptococcus : A literature review

Staudt,

Olivo,

Alves

et al. 2024

Braz. J. Pharm. Sci.

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“…Moreover, SRT effectively penetrates the blood–brain barrier to accumulate at high concentrations in the CNS [ 20 , 21 , 22 ]. Unfortunately, the results from clinical trials using therapeutic amounts of FLC with additional SRT during maintenance therapy indicate that SRT does not increase the efficacy of treatment [ 23 , 24 , 25 ], likely due to insufficient duration of therapeutic SRT concentrations.…”

Section: Introductionmentioning

confidence: 99%

The Antidepressant Sertraline Induces the Formation of Supersized Lipid Droplets in the Human Pathogen Cryptococcus neoformans

Breuer

Dasgupta

Vasselli

et al. 2022

JoF

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The prevalence and increasing incidence of fungal infections globally is a significant worldwide health problem. Cryptococcosis, primarily caused by the pathogenic yeast Cryptococcus neoformans, is responsible for approximately 181,000 estimated deaths annually. The scarcity of treatments and the increasing resistance to current therapeutics highlight the need for the development of antifungal agents which have novel mechanisms of action and are suitable for clinical use. Repurposing existing FDA-approved compounds as antimycotic therapeutics is a promising strategy for the rapid development of such new treatments. Sertraline (SRT), a commonly prescribed antidepressant, is a broad-spectrum antifungal agent with particular efficacy against C. neoformans. However, the effect of SRT on fungal physiology is not understood. Here, we report that SRT induces the formation of supersized lipid droplets (SLDs) in C. neoformans, and in Candida albicans, Saccharomyces cerevisiae, and Aspergillus fumigatus. SLDs were not induced in C. neoformans by treatment with the antifungal fluconazole (FLC), consistent with SRT and FLC acting differently to perturb C. neoformans physiology. The formation of SLDs in response to SRT indicates that this compound alters the lipid metabolism of C. neoformans. Moreover, the SRT-induced enlargement of LDs in other fungal species may indicate a common fungal response to SRT.

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Halal Alternative Formulation to Enhance Sertraline/Fluconazole Antifungal Activity and Minimize Drug Side Effect in Cryptococcus meningitis

Abualsunun,

Alzahrani,

Albaiti

et al. 2024

Solving Halal Industry Issues Through Research in Halal Sciences

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Pharmacokinetics-pharmacodynamics of sertraline as an antifungal in HIV-infected Ugandans with cryptococcal meningitis

Cited by 5 publications

References 48 publications

The role of modeling and simulation to improve the treatment of fungal infections caused by Cryptococcus : A literature review

The role of modeling and simulation to improve the treatment of fungal infections caused by Cryptococcus : A literature review

The Antidepressant Sertraline Induces the Formation of Supersized Lipid Droplets in the Human Pathogen Cryptococcus neoformans

Halal Alternative Formulation to Enhance Sertraline/Fluconazole Antifungal Activity and Minimize Drug Side Effect in Cryptococcus meningitis

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