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Amlodipine is a commonly prescribed antihypertensive drug metabolized by CYP3A4, thus predisposed to a risk of DDIs. Guidance on the management of DDIs is mostly based on theoretical considerations derived from coadministration with other CYP3A4 inhibitors. This study aimed at characterizing the magnitude of DDIs between amlodipine and ARV drugs in order to establish dosing recommendations.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A population pharmacokinetic analysis was developed using non-linear mixed effect modelling (NONMEM) and included 163 amlodipine concentrations from 55 PLWH. Various structural and error models were compared to characterize optimally the concentration-time profile of amlodipine. Demographic and clinical characteristics as well as comedications were tested as potential influential covariates. Model-based simulations were performed to compare amlodipine exposure (i.e. area under the curve, AUC) between coadministered ARV drugs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Amlodipine concentration-time profile was best described using a one-compartment model with first-order absorption and a lag-time. Amlodipine apparent clearance was influenced by both CYP3A4 inhibitors and efavirenz (CYP3A4 inducer). Model-based simulations revealed that amlodipine AUC increased by 96% when coadministered with CYP3A4 inhibitors, while efavirenz decreased drug exposure by 59%.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Coadministered ARV drugs significantly impact amlodipine disposition in PLWH. Clinicians should adjust amlodipine dosage accordingly, by halving the dosage in PLWH receiving ARV with inhibitory properties (mainly ritonavir-boosted darunavir), whereas they should double amlodipine doses when coadministering it with efavirenz, under appropriate monitoring of clinical response and tolerance.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00228-020-03060-2","type":"journal-article","created":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T03:02:31Z","timestamp":1610766151000},"page":"979-987","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Population pharmacokinetic modelling to quantify the magnitude of drug-drug interactions between amlodipine and antiretroviral drugs"],"prefix":"10.1007","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9114-7793","authenticated-orcid":false,"given":"Perrine","family":"Courlet","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6419-9317","authenticated-orcid":false,"given":"Monia","family":"Guidi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Alves Saldanha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0933-7833","authenticated-orcid":false,"given":"Matthias","family":"Cavassini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel","family":"Stoeckle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0639-5536","authenticated-orcid":false,"given":"Thierry","family":"Buclin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2312-7050","authenticated-orcid":false,"given":"Catia","family":"Marzolini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9840-1325","authenticated-orcid":false,"given":"Laurent A.","family":"Decosterd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0660-082X","authenticated-orcid":false,"given":"Chantal","family":"Csajka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,16]]},"reference":[{"issue":"2","key":"3060_CR1","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.clpt.2005.04.005","volume":"78","author":"MJ Glesby","year":"2005","unstructured":"Glesby MJ, Aberg JA, Kendall MA, Fichtenbaum CJ, Hafner R, Hall S, Grosskopf N, Zolopa AR, Gerber JG, Adult ACTGAPT (2005) Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers. 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MS received payments for advisory boards from Gilead, ViiV, MSD, Sandoz and Mepha, as well as travel grants for conferences from Gilead and MSD, yet unrelated to the present study. CM received a research grant from Gilead and speaker honoraria for her institution from MSD. All other authors: none to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The protocol of the study with rich sampling was reviewed and approved by the Ethics Committee of Vaud and northwest\/central Switzerland (CER-VD 2018\u201300369).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent was obtained from each patient participating in the study with rich sampling.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}}]}}