PBPK Modeling to Recommend Nevirapine Dosing in HIV and HIV-TB Co-infected Patients: Leveraging Enzyme Auto-Induction, Drug Interactions, and Ethnic Variability

Havlir DV, Getahun H, Sanne I, Nunn P. Opportunities and challenges for HIV care in overlapping HIV and TB epidemics. JAMA. 2008;300(4):423–30.

CAS  PubMed  Google Scholar 

Lawn SD, Churchyard G. Epidemiology of HIV-associated tuberculosis. Curr Opin HIV AIDS. 2009;4(4):325–33.

PubMed  PubMed Central  Google Scholar 

WHO: Global Tuberculosis Report 2023. https://www.who.int/publications/m/item/top-findings-and-messages-gtb2023. Accessed 6 November 2023.

Trinh QM, Nguyen HL, Nguyen VN, Nguyen TV, Sintchenko V, Marais BJ. Tuberculosis and HIV co-infection-focus on the Asia-Pacific region. Int J Infect Dis. 2015;32:170–8.

CAS  PubMed  Google Scholar 

Navasardyan I, Miwalian R, Petrosyan A, Yeganyan S, Venketaraman V. HIV-TB Coinfection: Current Therapeutic Approaches and Drug Interactions. Viruses. 2024;16(3):321.

CAS  PubMed  PubMed Central  Google Scholar 

Avihingsanon A, Manosuthi W, Kantipong P, Chuchotaworn C, Moolphate S, Sakornjun W, et al. Pharmacokinetics and 48-week efficacy of nevirapine: 400 mg versus 600 mg per day in HIV-tuberculosis coinfection receiving rifampicin. Antivir Ther. 2008;13(4):529–36.

CAS  PubMed  Google Scholar 

van Leth F, Phanuphak P, Ruxrungtham K, Baraldi E, Miller S, Gazzard B, et al. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. Lancet. 2004;363(9417):1253–63.

PubMed  Google Scholar 

Riska P, Lamson M, MacGregor T, Sabo J, Hattox S, Pav J, et al. Disposition and biotransformation of the antiretroviral drug nevirapine in humans. Drug Metab Dispos. 1999;27(8):895–901.

CAS  PubMed  Google Scholar 

Erickson DA, Mather G, Trager WF, Levy RH, Keirns JJ. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. Drug Metab Dispos. 1999;27(12):1488–95.

CAS  PubMed  Google Scholar 

Gopalan BP, Mehta K, D'Souza R R, Rajnala N, A KH, Ramachandran G, et al. Sub-therapeutic nevirapine concentration during antiretroviral treatment initiation among children living with HIV: Implications for therapeutic drug monitoring. PLoS One. 2017;12(8):e0183080.

Lamson M, MacGregor T, Riska P, Erickson D, Maxfield P, Rowland L, et al. Nevirapine Induces Both CYP3A4 and CYP2B6 Metabolic Pathways. Clin Pharmacol Ther. 1999;65(2):137.

Google Scholar 

Rae JM, Johnson MD, Lippman ME, Flockhart DA. Rifampin is a selective, pleiotropic inducer of drug metabolism genes in human hepatocytes: studies with cDNA and oligonucleotide expression arrays. J Pharmacol Exp Ther. 2001;299(3):849–57.

CAS  PubMed  Google Scholar 

Burman WJ, Jones BE. Treatment of HIV-related tuberculosis in the era of effective antiretroviral therapy. Am J Respir Crit Care Med. 2001;164(1):7–12.

CAS  PubMed  Google Scholar 

Elsherbiny D, Cohen K, Jansson B, Smith P, McIlleron H, Simonsson US. Population pharmacokinetics of nevirapine in combination with rifampicin-based short course chemotherapy in HIV- and tuberculosis-infected South African patients. Eur J Clin Pharmacol. 2009;65(1):71–80.

CAS  PubMed  Google Scholar 

Olafuyi O, Coleman M, Badhan RKS. Development of a paediatric physiologically based pharmacokinetic model to assess the impact of drug-drug interactions in tuberculosis co-infected malaria subjects: A case study with artemether-lumefantrine and the CYP3A4-inducer rifampicin. Eur J Pharm Sci. 2017;106:20–33.

CAS  PubMed  Google Scholar 

Wen X, Wang JS, Neuvonen PJ, Backman JT. Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes. Eur J Clin Pharmacol. 2002;57(11):799–804.

PubMed  Google Scholar 

Dailly E, Billaud E, Reliquet V, Breurec S, Perré P, Léautez S, et al. No relationship between high nevirapine plasma concentration and hepatotoxicity in HIV-1-infected patients naive of antiretroviral treatment or switched from protease inhibitors. Eur J Clin Pharmacol. 2004;60(5):343–8.

CAS  PubMed  Google Scholar 

de Maat MM, Huitema AD, Mulder JW, Meenhorst PL, van Gorp EC, Beijnen JH. Population pharmacokinetics of nevirapine in an unselected cohort of HIV-1-infected individuals. Br J Clin Pharmacol. 2002;54(4):378–85.

PubMed  PubMed Central  Google Scholar 

Kappelhoff BS, van Leth F, MacGregor TR, Lange J, Beijnen JH, Huitema AD. Nevirapine and efavirenz pharmacokinetics and covariate analysis in the 2NN study. Antivir Ther. 2005;10(1):145–55.

CAS  PubMed  Google Scholar 

Wattanakul T, Avihingsanon A, Manosuthi W, Punyawudho B. Population pharmacokinetics of nevirapine in Thai HIV-infected patients. Antivir Ther. 2014;19(7):651–60.

CAS  PubMed  Google Scholar 

Kappelhoff BS, Crommentuyn KM, de Maat MM, Mulder JW, Huitema AD, Beijnen JH. Practical guidelines to interpret plasma concentrations of antiretroviral drugs. Clin Pharmacokinet. 2004;43(13):845–53.

CAS  PubMed  Google Scholar 

Ramachandran G, Hemanthkumar AK, Rajasekaran S, Padmapriyadarsini C, Narendran G, Sukumar B, et al. Increasing nevirapine dose can overcome reduced bioavailability due to rifampicin coadministration. J Acquir Immune Defic Syndr. 2006;42(1):36–41.

CAS  PubMed  Google Scholar 

Autar RS, Wit FW, Sankote J, Mahanontharit A, Anekthananon T, Mootsikapun P, et al. Nevirapine plasma concentrations and concomitant use of rifampin in patients coinfected with HIV-1 and tuberculosis. Antivir Ther. 2005;10(8):937–43.

CAS  PubMed  Google Scholar 

Cohen K, van Cutsem G, Boulle A, McIlleron H, Goemaere E, Smith PJ, et al. Effect of rifampicin-based antitubercular therapy on nevirapine plasma concentrations in South African adults with HIV-associated tuberculosis. J Antimicrob Chemother. 2008;61(2):389–93.

CAS  PubMed  Google Scholar 

de Vries-Sluijs TE, Dieleman JP, Arts D, Huitema AD, Beijnen JH, Schutten M, et al. Low nevirapine plasma concentrations predict virological failure in an unselected HIV-1-infected population. Clin Pharmacokinet. 2003;42(6):599–605.

PubMed  Google Scholar 

Kwara A, Ramachandran G, Swaminathan S. Dose adjustment of the non-nucleoside reverse transcriptase inhibitors during concurrent rifampicin-containing tuberculosis therapy: one size does not fit all. Expert Opin Drug Metab Toxicol. 2010;6(1):55–68.

CAS  PubMed  PubMed Central  Google Scholar 

Rowland M, Balant L, Peck C. Physiologically based pharmacokinetics in drug development and regulatory science: a workshop report (Georgetown University, Washington, DC, May 29–30, 2002). AAPS PharmSci. 2004;6(1):E6.

PubMed  Google Scholar 

Cramer YS, Rosenkranz SL, Hall SD, Szczech LA, Amorosa V, Gupta SK. Hemodialysis does not significantly affect the pharmacokinetics of nevirapine in HIV-1-infected persons requiring hemodialysis: results from ACTG A5177. J Acquir Immune Defic Syndr. 2010;54(4):e7-9.

PubMed  PubMed Central  Google Scholar 

De Sousa MM, Lui G, Zheng Y, Pressiat C, Hirt D, Valade E, et al. A Physiologically-Based Pharmacokinetic Model to Predict Human Fetal Exposure for a Drug Metabolized by Several CYP450 Pathways. Clin Pharmacokinet. 2017;56(5):537–50.

Google Scholar 

Zhu Y, Zhang Q, Yu C, Zou J, Yang X, Hu Y. Relative bioavailability of two formulations of nevirapine 200-mg tablets in healthy Chinese male volunteers: A single-dose, randomized-sequence, open-label, two-way crossover study. Clin Ther. 2010;32(13):2258–64.

CAS  PubMed  Google Scholar 

Lamson MJ, Sabo JP, MacGregor TR, Pav JW, Rowland L, Hawi A, et al. Single dose pharmacokinetics and bioavailability of nevirapine in healthy volunteers. Biopharm Drug Dispos. 1999;20(6):285–91.

CAS  PubMed  Google Scholar 

van Heeswijk RP, Veldkamp AI, Mulder JW, Meenhorst PL, Wit FW, Lange JM, et al. The steady-state pharmacokinetics of nevirapine during once daily and twice daily dosing in HIV-1-infected individuals. AIDS. 2000;14(8):F77-82.

PubMed  Google Scholar 

Faucette SR, Zhang TC, Moore R, Sueyoshi T, Omiecinski CJ, LeCluyse EL, et al. Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers. J Pharmacol Exp Ther. 2007;320(1):72–80.

CAS  PubMed  Google Scholar 

Amaeze OU, Isoherranen N. Application of a physiologically based pharmacokinetic model to predict isoniazid disposition during pregnancy. Clin Transl Sci. 2023;16(11):2163–76.

CAS  PubMed  PubMed Central  Google Scholar 

Kubota R, Ohno M, Hasunuma T, Iijima H, Azuma J. Dose-escalation study of isoniazid in healthy volunteers with the rapid acetylator genotype of arylamine N-acetyltransferase 2. Eur J Clin Pharmacol. 2007;63(10):927–33.

CAS  PubMed  Google Scholar 

Matteelli A, Saleri N, Villani P, Bonkoungou V, Carvalho AC, Kouanda S, et al. Reversible reduction of nevirapine plasma concentrations during rifampicin treatment in patients coinfected with HIV-1 and tuberculosis. J Acquir Immune Defic Syndr. 2009;52(1):64–9.

CAS  PubMed  Google Scholar 

Ribera E, Pou L, Lopez RM, Crespo M, Falco V, Ocaña I, et al. Pharmacokinetic interaction between nevirapine and rifampicin in HIV-infected patients with tuberculosis. J Acquir Immune Defic Syndr. 2001;28(5):450–3.

CAS  PubMed  Google Scholar 

Ke A, Barter Z, Rowland-Yeo K, Almond L. Towards a Best Practice Approach in PBPK Modeling: Case Example of Developing a Unified Efavirenz Model Accounting for Induction of CYPs 3A4 and 2B6. CPT Pharmacometrics Syst Pharmacol. 2016;5(7):367–76.

CAS  PubMed  PubMed Central 

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