Older Age is Associated with Higher Dolutegravir Exposure in Plasma and Cerebrospinal Fluid of People Living with HIV
| العنوان: | Older Age is Associated with Higher Dolutegravir Exposure in Plasma and Cerebrospinal Fluid of People Living with HIV |
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| المؤلفون: | Antonio D'Avolio, Simona Di Giambenedetto, Mattia Trunfio, José Moltó, Maurizio Milesi, Cristina Gervasoni, Stefano Bonora, Francesc Pla-Junca, Marta Valle, Alberto Borghetti, Valeria Avataneo, Chiara Alcantarini, Dario Cattaneo, Giovanni Di Perri, Andrea Calcagno |
| المصدر: | CLINICAL PHARMACOKINETICS r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname r-IIB SANT PAU: Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau Institut dInvestigació Biomèdica Sant Pau (IIB Sant Pau) Clinical Pharmacokinetics r-IGTP: Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol Institut de Recerca Germans Trias i Pujol (IGTP) r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol Universidad de Alicante (UA) |
| بيانات النشر: | ADIS INT LTD, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, medicine.medical_specialty, Pyridones, 030106 microbiology, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, 3-Ring, Settore MED/17 - MALATTIE INFETTIVE, Gastroenterology, Piperazines, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pharmacotherapy, Cerebrospinal fluid, Heterocyclic Compounds, Internal medicine, Oxazines, medicine, Humans, Pharmacology (medical), Trough Concentration, 030212 general & internal medicine, HIV Integrase Inhibitors, Retrospective Studies, Pharmacology, medicine.diagnostic_test, business.industry, Age Factors, Middle Aged, chemistry, Ageing, Therapeutic drug monitoring, Concomitant, Dolutegravir, Female, business, Heterocyclic Compounds, 3-Ring |
| الوصف: | Background People living with human immunodeficiency virus are ageing under combination antiretroviral treatments but data on drug exposure in serum and cerebrospinal fluid are limited. Dolutegravir is a widely used second-generation integrase strand transfer inhibitor: conflicting data suggest that neuropsychiatric side effects may present at a higher frequency in patients with higher dolutegravir serum concentrations. Methods We performed a retrospective analysis of our therapeutic drug monitoring registry identifying patients receiving once-daily dolutegravir without concomitant interacting drugs and significant clinical conditions. Data were analysed stratifying time after drug dose intake (maximum concentration 0.5-4 and trough concentration 21-27 h). Cerebrospinal fluid samples from patients enrolled in neurological studies and receiving dolutegravir were analysed for dolutegravir cerebrospinal fluid concentrations and cerebrospinal fluid-to-plasma ratios. Serum and cerebrospinal fluid concentrations were measured through validated chromatographic methods. Results We included 207 (providing 457 serum samples) and 41 patients (providing 41 cerebrospinal fluid samples). Participants were mostly male (68.2-72.8%) of median age of 50 years (50-53 years). Non-significant changes in dolutegravir maximum concentration and trough concentration were observed with age at Spearman's test (pvalues > 0.05); linear logistic regression showed a significant effect of age on dolutegravir trough concentration (p = 0.0013) (Fig. 1). Dolutegravir maximum concentration [3830 ng/mL (2311-5057) vs 4230 ng/mL (2919-5272),p = 0.311] and trough concentration [838 ng/mL (362-1587) vs 966 ng/mL (460-2085),p = 0.056] were non-significantly or borderline higher in patients aged > 50 years. Cerebrospinal dolutegravir concentrations were associated with plasma concentrations (rho = 0.374,p = 0.016) and age (rho = 0.537,p = 0.003); cerebrospinal fluid dolutegravir concentrations (13.8 vs 7.3 ng/mL,p = 0.015) and cerebrospinal fluid-to-plasma ratios (0.57 vs 0.32%,p = 0.017] were higher in participants aged > 50 years. Conclusions We observed an increase in dolutegravir exposure in serum and in cerebrospinal fluid in older patients living with human immunodeficiency virus. |
| تدمد: | 0312-5963 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aaaff9c375efef7a2990b9db68301b22Test https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1404Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....aaaff9c375efef7a2990b9db68301b22 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 03125963 |
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