Population pharmacokinetic modelling to quantify the magnitude of drug-drug interactions between amlodipine and antiretroviral drugs.
Aged
Amlodipine
/ pharmacokinetics
Anti-Retroviral Agents
/ pharmacology
Antihypertensive Agents
/ pharmacokinetics
Area Under Curve
Cytochrome P-450 CYP3A
/ pharmacology
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 CYP3A Inhibitors
/ pharmacology
Drug Interactions
Female
Humans
Male
Middle Aged
Models, Biological
Socioeconomic Factors
Amlodipine
Drug-drug interactions
HIV
NONMEM
Pharmacokinetics
Journal
European journal of clinical pharmacology
ISSN: 1432-1041
Titre abrégé: Eur J Clin Pharmacol
Pays: Germany
ID NLM: 1256165
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
17
09
2020
accepted:
26
11
2020
pubmed:
17
1
2021
medline:
20
11
2021
entrez:
16
1
2021
Statut:
ppublish
Résumé
Drug-drug interactions (DDIs) with antiretroviral drugs (ARVs) represent an important issue in elderly people living with HIV (PLWH). 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. 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. 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%. 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.
Identifiants
pubmed: 33452585
doi: 10.1007/s00228-020-03060-2
pii: 10.1007/s00228-020-03060-2
pmc: PMC8184532
doi:
Substances chimiques
Anti-Retroviral Agents
0
Antihypertensive Agents
0
Cytochrome P-450 CYP3A Inducers
0
Cytochrome P-450 CYP3A Inhibitors
0
Amlodipine
1J444QC288
Cytochrome P-450 CYP3A
EC 1.14.14.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
979-987Subventions
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CH)
ID : 165956
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CH)
ID : 166204
Références
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. Clin Pharmacol Ther 78(2):143–153. https://doi.org/10.1016/j.clpt.2005.04.005
doi: 10.1016/j.clpt.2005.04.005
pubmed: 16084849
Lee JE, van Heeswijk R, Alves K, Smith F, Garg V (2011) Effect of the hepatitis C virus protease inhibitor telaprevir on the pharmacokinetics of amlodipine and atorvastatin. Antimicrob Agents Chemother 55(10):4569–4574. https://doi.org/10.1128/AAC.00653-11
doi: 10.1128/AAC.00653-11
pubmed: 21825288
pmcid: 3187007
Meredith PA, Elliott HL (1992) Clinical pharmacokinetics of amlodipine. Clin Pharmacokinet 22(1):22–31. https://doi.org/10.2165/00003088-199222010-00003
doi: 10.2165/00003088-199222010-00003
pubmed: 1532771
Food and Drug Administration. Norvasc, Summary of Product Characteristics. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf . Accessed 7 June 2019
Menon RM, Badri PS, Wang T, Polepally AR, Zha J, Khatri A, Wang H, Hu B, Coakley EP, Podsadecki TJ, Awni WM, Dutta S (2015) Drug-drug interaction profile of the all-oral anti-hepatitis C virus regimen of paritaprevir/ritonavir, ombitasvir, and dasabuvir. J Hepatol 63(1):20–29. https://doi.org/10.1016/j.jhep.2015.01.026
doi: 10.1016/j.jhep.2015.01.026
pubmed: 25646891
Flynn JT, Nahata MC, Mahan JD Jr, Portman RJ, Investigators P (2006) Population pharmacokinetics of amlodipine in hypertensive children and adolescents. J Clin Pharmacol 46(8):905–916. https://doi.org/10.1177/0091270006289844
doi: 10.1177/0091270006289844
pubmed: 16855075
Heo YA, Holford N, Kim Y, Son M, Park K (2016) Quantitative model for the blood pressure-lowering interaction of valsartan and amlodipine. Br J Clin Pharmacol 82(6):1557–1567. https://doi.org/10.1111/bcp.13082
doi: 10.1111/bcp.13082
pubmed: 27504853
pmcid: 5099563
Kang D, Verotta D, Schwartz JB (2006) Population analyses of amlodipine in patients living in the community and patients living in nursing homes. Clin Pharmacol Ther 79(1):114–124. https://doi.org/10.1016/j.clpt.2005.09.007
doi: 10.1016/j.clpt.2005.09.007
pubmed: 16413246
Rohatagi S, Carrothers TJ, Kshirsagar S, Khariton T, Lee J, Salazar D (2008) Evaluation of population pharmacokinetics and exposure-response relationship with coadministration of amlodipine besylate and olmesartan medoxomil. J Clin Pharmacol 48(7):823–836. https://doi.org/10.1177/0091270008317847
doi: 10.1177/0091270008317847
pubmed: 18490496
Son H, Lee D, Lim LA, Jang SB, Roh H, Park K (2014) Development of a pharmacokinetic interaction model for co-administration of simvastatin and amlodipine. Drug Metab Pharmacokinet 29(2):120–128
doi: 10.2133/dmpk.DMPK-13-RG-053
Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1):31–41. https://doi.org/10.1159/000180580
doi: 10.1159/000180580
pubmed: 1244564
Courlet P, Spaggiari D, Desfontaine V, Cavassini M, Alves Saldanha S, Buclin T, Marzolini C, Csajka C, Decosterd LA (2019) UHPLC-MS/MS assay for simultaneous determination of amlodipine, metoprolol, pravastatin, rosuvastatin, atorvastatin with its active metabolites in human plasma, for population-scale drug-drug interactions studies in people living with HIV. J Chromatogr B Anal Technol Biomed Life Sci 1125:121733. https://doi.org/10.1016/j.jchromb.2019.121733
doi: 10.1016/j.jchromb.2019.121733
Choi Y, Lee S, Cho SM, Kang WH, Nam KY, Jang IJ, Yu KS (2016) Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study. Drug Des Devel Ther 10:3021–3028. https://doi.org/10.2147/DDDT.S113891
doi: 10.2147/DDDT.S113891
pubmed: 27703330
pmcid: 5036556
Zarghi A, Foroutan SM, Shafaati A, Khoddam A (2005) Validated HPLC method for determination of amlodipine in human plasma and its application to pharmacokinetic studies. Farmaco 60(9):789–792. https://doi.org/10.1016/j.farmac.2005.06.012
doi: 10.1016/j.farmac.2005.06.012
pubmed: 16038908
Lindbom L, Pihlgren P, Jonsson EN (2005) PsN-toolkit--a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM. Comput Methods Prog Biomed 79(3):241–257. https://doi.org/10.1016/j.cmpb.2005.04.005
doi: 10.1016/j.cmpb.2005.04.005
Keizer RJ, van Benten M, Beijnen JH, Schellens JH, Huitema AD (2011) Pirana and PCluster: a modeling environment and cluster infrastructure for NONMEM. Comput Methods Prog Biomed 101(1):72–79. https://doi.org/10.1016/j.cmpb.2010.04.018
doi: 10.1016/j.cmpb.2010.04.018
Food and drug administration. Drug development and drug interactions: table of substrates, inhibitors and inducers. https://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm . Accessed 20 Dec 2018
Duffull SB, Wright DF, Winter HR (2011) Interpreting population pharmacokinetic-pharmacodynamic analyses - a clinical viewpoint. Br J Clin Pharmacol 71(6):807–814. https://doi.org/10.1111/j.1365-2125.2010.03891.x
doi: 10.1111/j.1365-2125.2010.03891.x
pubmed: 21204908
pmcid: 3099367
Gab-jin P, Dooyeon J, Jong nyeong K, Sunil Y, Wan-Su P, Jongtae L, Seunghoon H, Dong-Seok Y (2015) Drug-drug interaction analysis of a drug with long elimination half-life using population pharmacokinetic approach. Paper presented at the Population Approach Group in Europe, Hersonissos
Suein C, Seunghoon H, Dong-Seok Y (2019) Contribution of trough concentration data for the evaluation of multiple-dose pharmacokinetics. Paper presented at the Population approach group in Europe, Stockholm, 11–14.06.2019
Mukherjee D, Zha J, Menon RM, Shebley M (2018) Guiding dose adjustment of amlodipine after co-administration with ritonavir containing regimens using a physiologically-based pharmacokinetic/pharmacodynamic model. J Pharmacokinet Pharmacodyn 45(3):443–456. https://doi.org/10.1007/s10928-018-9574-0
doi: 10.1007/s10928-018-9574-0
pubmed: 29427135
pmcid: 5953987
Stader F, Courlet P, Kinvig H, Penny MA, Decosterd LA, Battegay M, Siccardi M, Marzolini C (2020) Clinical data combined with modelling and simulation indicate unchanged drug-drug interaction magnitudes in the elderly. Clin Pharmacol Ther. https://doi.org/10.1002/cpt.2017
Bleyzac N, Bourguignon L, Goutelle S, Tod MDDI. Impact of drug-drug interactions of drug exposure https://www.ddi-predictor.org/predictor/ddi
Stader F, Kinvig H, Battegay M, Khoo S, Owen A, Siccardi M, Marzolini C (2018) Analysis of clinical drug-drug interaction data to predict magnitudes of uncharacterized interactions between antiretroviral drugs and comedications. Antimicrob Agents Chemother 62(7):e00717–e00718. https://doi.org/10.1128/AAC.00717-18
doi: 10.1128/AAC.00717-18
pubmed: 29686151
pmcid: 6021627
Marzolini C, Gibbons S, Khoo S, Back D (2016) Cobicistat versus ritonavir boosting and differences in the drug-drug interaction profiles with co-medications. J Antimicrob Chemother 71(7):1755–1758. https://doi.org/10.1093/jac/dkw032
doi: 10.1093/jac/dkw032
pubmed: 26945713
Liverpool HIV drug interactions website. http://www.hiv-druginteractions.org/ . Accessed 16.07.2019
Izzedine H, Launay-Vacher V, Deray G, Hulot JS (2004) Nelfinavir and felodipine: a cytochrome P450 3A4-mediated drug interaction. Clin Pharmacol Ther 75(4):362–363. https://doi.org/10.1016/j.clpt.2003.12.006
doi: 10.1016/j.clpt.2003.12.006
pubmed: 15060514
Puech R, Gagnieu MC, Planus C, Charpiat B, Boibieux A, Ferry T, Tod M (2011) Extreme bradycardia due to multiple drug-drug interactions in a patient with HIV post-exposure prophylaxis containing lopinavir-ritonavir. Br J Clin Pharmacol 71(4):621–623. https://doi.org/10.1111/j.1365-2125.2010.03849.x
doi: 10.1111/j.1365-2125.2010.03849.x
pubmed: 21395657
pmcid: 3080653
Baeza MT, Merino E, Boix V, Climent E (2007) Nifedipine-lopinavir/ritonavir severe interaction: a case report. Aids 21(1):119–120. https://doi.org/10.1097/QAD.0b013e3280117f6f
doi: 10.1097/QAD.0b013e3280117f6f
pubmed: 17148983
Kader C, Ede H, Erbay A, Erbay A (2015) Drug interaction of boceprevir and amlodipine in a patient with hepatitis C: a cardiovascular follow-up. J Microbiol Infect Dis 5(1):32–35. https://doi.org/10.5799/ahinjs.02.2015.01.0172
doi: 10.5799/ahinjs.02.2015.01.0172
Molto J, Rajoli R, Back D, Valle M, Miranda C, Owen A, Clotet B, Siccardi M (2017) Use of a physiologically based pharmacokinetic model to simulate drug-drug interactions between antineoplastic and antiretroviral drugs. J Antimicrob Chemother 72(3):805–811. https://doi.org/10.1093/jac/dkw485
doi: 10.1093/jac/dkw485
pubmed: 27999009
Kapetas AJ, Sorich MJ, Rodrigues AD, Rowland A (2019) Guidance for rifampin and midazolam dosing protocols to study intestinal and hepatic cytochrome P450 (CYP) 3A4 induction and De-induction. AAPS J 21(5):78. https://doi.org/10.1208/s12248-019-0341-y
doi: 10.1208/s12248-019-0341-y
pubmed: 31218462
Leenen FH, Coletta E (2010) Pharmacokinetic and antihypertensive profile of amlodipine and felodipine-ER in younger versus older patients with hypertension. J Cardiovasc Pharmacol 56(6):669–675. https://doi.org/10.1097/FJC.0b013e3181fc45bb
doi: 10.1097/FJC.0b013e3181fc45bb
pubmed: 20881606
Flexner C, Tierney C, Gross R, Andrade A, Lalama C, Eshleman SH, Aberg J, Sanne I, Parsons T, Kashuba A, Rosenkranz SL, Kmack A, Ferguson E, Dehlinger M, Mildvan D, Team AAS (2010) Comparison of once-daily versus twice-daily combination antiretroviral therapy in treatment-naive patients: results of AIDS clinical trials group (ACTG) A5073, a 48-week randomized controlled trial. Clin Infect Dis 50(7):1041–1052. https://doi.org/10.1086/651118
doi: 10.1086/651118
pubmed: 20192725
pmcid: 2833234
Kamal S, Bugnon O, Cavassini M, Schneider MP (2018) HIV-infected patients' beliefs about their chronic co-treatments in comparison with their combined antiretroviral therapy. HIV Med 19(1):49–58. https://doi.org/10.1111/hiv.12542
doi: 10.1111/hiv.12542
pubmed: 28815917
Song I, Borland J, Min S, Lou Y, Chen S, Patel P, Wajima T, Piscitelli SC (2011) Effects of etravirine alone and with ritonavir-boosted protease inhibitors on the pharmacokinetics of dolutegravir. Antimicrob Agents Chemother 55(7):3517–3521. https://doi.org/10.1128/AAC.00073-11
doi: 10.1128/AAC.00073-11
pubmed: 21555764
pmcid: 3122457
Hafner V, Jager M, Matthee AK, Ding R, Burhenne J, Haefeli WE, Mikus G (2010) Effect of simultaneous induction and inhibition of CYP3A by St John's Wort and ritonavir on CYP3A activity. Clin Pharmacol Ther 87(2):191–196. https://doi.org/10.1038/clpt.2009.206
doi: 10.1038/clpt.2009.206
pubmed: 19924124
Duval X, Le Moing V, Longuet C, Leport C, Vilde JL, Lamotte C, Peytavin G, Farinotti R (2000) Efavirenz-induced decrease in plasma amprenavir levels in human immunodeficiency virus-infected patients and correction by ritonavir. Antimicrob Agents Chemother 44(9):2593. https://doi.org/10.1128/aac.44.9.2593-2593.2000
doi: 10.1128/aac.44.9.2593-2593.2000
pubmed: 11012391
pmcid: 90119
Abel S, Jenkins TM, Whitlock LA, Ridgway CE, Muirhead GJ (2008) Effects of CYP3A4 inducers with and without CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol 65(Suppl 1):38–46. https://doi.org/10.1111/j.1365-2125.2008.03134.x
doi: 10.1111/j.1365-2125.2008.03134.x
pubmed: 18333864
pmcid: 2311410
Kakuda TN, Abel S, Davis J, Hamlin J, Scholler-Gyure M, Mack R, Ndongo N, Petit W, Ridgway C, Sekar V, Tweedy S, Hoetelmans RM (2011) Pharmacokinetic interactions of maraviroc with darunavir-ritonavir, etravirine, and etravirine-darunavir-ritonavir in healthy volunteers: results of two drug interaction trials. Antimicrob Agents Chemother 55(5):2290–2296. https://doi.org/10.1128/AAC.01046-10
doi: 10.1128/AAC.01046-10
pubmed: 21383098
pmcid: 3088221
Wade JR, Beal SL, Sambol NC (1994) Interaction between structural, statistical, and covariate models in population pharmacokinetic analysis. J Pharmacokinet Biopharm 22(2):165–177. https://doi.org/10.1007/bf02353542
doi: 10.1007/bf02353542
pubmed: 7815312
Tseng A, Hughes CA, Wu J, Seet J, Phillips EJ (2017) Cobicistat versus ritonavir: similar pharmacokinetic enhancers but some important differences. Ann Pharmacother 51(11):1008–1022. https://doi.org/10.1177/1060028017717018
doi: 10.1177/1060028017717018
pubmed: 28627229
pmcid: 5702580