Kajian Literatur Profil Farmakokinetika Sacubitril-Valsartan Pada Subjek Sehat dan Gagal Jantung

Firda Amelya; Ratih Aryani; Fetri Lestari

doi:10.29313/bcsp.v3i2.8536

Firda Amelya Farmasi
Ratih Aryani Farmasi
Fetri Lestari Universitas Islam Bandung

DOI: https://doi.org/10.29313/bcsp.v3i2.8536

Keywords: Farmakokinetika, Sacubitril-Valsartan, Gagal Jantung

Abstract

Abstract. Sacubitril-Valsartan is a first-class therapeutic agent for ARNI (Angiotensin Receptor-Neprilysin Inhibitor) which can reduce blood pressure and reduce mortality and morbidity in patients with Heart failure with Reduced Ejection Fraction (HFrEF). A combination of Neprilysin inhibitors (NEPi) and Angiotensin II Receptor Blockers (ARBs) is required to reduce the increased bradykinin concentrations due to neprilysin inhibition. The success of Sacubitril-Valsartan therapy is determined by the dosage setting design taking into account pharmacokinetic factors. The pharmacokinetic profile of each individual may vary, influenced by differences in race/ethnicity, gender, age, drug interactions and physiological changes. This study aims to determine the pharmacokinetic parameters of the drug Sacubitril-Valsartan based on differences in race/ethnicity, sex, age, drug interactions, in subjects with impaired kidney function, and in subjects with heart failure. The method used for this study is the SLR (Systematic Literature Review) method. The articles used in this study were 10 journal articles obtained from the PMC database, Wiley, Springer Link. The results showed that race/ethnicity affects T1/2 longer in Caucasians, female sex has a longer T1/2, older people have a longer T1/2, Cmax, T1/2, AUC_0-24h increased in impaired kidney function with decreased CL, Cmax and T1/2 increased in HFREF patients.

Keywords: Pharmacokinetic, Sacubitril-Valsartan, Heart failure.

Abstrak. Sacubitril-Valsartan merupakan agen terapeutik kelas pertama ARNI (Angiotensin Reseptor-Neprilysin Inhibitor) yang dapat menurunkan tekanan darah dan menurunkan mortalitas dan morbiditas pada pasien Heart failure with Reduced Ejection Fraction (HFrEF). Kombinasi Neprilysin inhibitor (NEPi) dan Angiotensin II Receptor Blockers (ARB) diperlukan untuk mengurangi konsentrasi bradikinin yang meningkat akibat penghambatan neprilysin. Keberhasilan terapi Sacubitril-Valsartan ditentukan oleh rancangan pengaturan dosis dengan mempertimbangkan faktor farmakokinetika. Profil farmakokinetika pada setiap individu dapat bervariasi dipengaruhi oleh perbedaan ras/etnis, jenis kelamin, usia, interaksi obat-obatan dan perubahan fisiologi. Penelitian ini bertujuan untuk mengetahui parameter farmakokinetika obat Sacubitril-Valsartan berdasarkan perbedaan ras/etnis, jenis kelamin, usia, interaksi obat-obatan, pada subjek dengan gangguan fungsi ginjal, dan pada subjek gagal jantung. Metode yang digunakan untuk penelitian ini adalah metode SLR (Systematic Literature Review). Artikel yang digunakan pada penelitian ini sebanyak 10 artikel jurnal yang diperoleh dari database PMC, Wiley, Springer Link. Hasil penelitian menunjukan bahwa ras/etnis mempengaruhi T1/2 lebih lama pada ras Kaukasia, jenis kelamin perempuan memiliki T1/2 lebih lama, usia tua memiliki T1/2 lebih lama, Cmax, T1/2, AUC_0-24jam meningkat pada subjek gangguan fungsi ginjal dengan CL yang menurun, Cmax dan T1/2 meningkat pada pasien HFREF.

Kata Kunci: Farmakokinetika, Sacubitril-Valsartan, Gagal Jantung.

References

[1] PERKI, “Pedoman Tatalaksana Gagal Jantung 2020. 2nd ed.,” Perhimpunan. Dr. Spes. Kardiovask. Indones. 2020, vol. 6, no. 11, pp. 951–952, 2020.
[2] S. J. Simmonds, I. Cuijpers, S. Heymans, and E. A. V. Jones, “Cellular and Molecular Differences between HFpEF and HFrEF: A Step Ahead in an Improved Pathological Understanding,” Cells, vol. 9, no. 1, 2020, doi: 10.3390/cells9010242.
[3] M. B. Andersen, U. Simonsen, M. Wehland, J. Pietsch, and D. Grimm, “LCZ696 (Valsartan/Sacubitril) - A Possible New Treatment for Hypertension and Heart Failure,” Basic Clin. Pharmacol. Toxicol., vol. 118, no. 1, pp. 14–22, 2016, doi: 10.1111/bcpt.12453.
[4] A. Bayes-Genis, J. Núñez, and J. Lupón, “Sacubitril/Valsartan as Antifibrotic Drug: Rejuvenating the Fibrosed HFpEF Heart,” J. Am. Coll. Cardiol., vol. 76, no. 5, pp. 515–517, 2020, doi: 10.1016/j.jacc.2020.06.016.
[5] N. Farid, “Recent Advances in Pharmacokinetics and Its Implications,” vol. 10, no. 1000392, p. 1000392, 2022, doi: 10.35248/2329-6887.22.10.392.Citation.
[6] T. N. Lea-Henry, J. E. Carland, S. L. Stocker, J. Sevastos, and D. M. Roberts, “Clinical pharmacokinetics in kidney disease: Fundamental principles,” Clin. J. Am. Soc. Nephrol., vol. 13, no. 7, pp. 1085–1095, 2018, doi: 10.2215/CJN.00340118.
[7] Y. Han et al., “Pharmacokinetics, Safety and Tolerability of Sacubitril/Valsartan (LCZ696) After Single-Dose Administration in Healthy Chinese Subjects,” Eur. J. Drug Metab. Pharmacokinet., vol. 42, no. 1, pp. 109–116, 2017, doi: 10.1007/s13318-016-0328-3.
[8] J. Gu et al., “Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi).,” J. Clin. Pharmacol., vol. 50, no. 4, pp. 401–414, 2010, doi: 10.1177/0091270009343932.
[9] L. Gan et al., “Effects of age and sex on the pharmacokinetics of LCZ696, an angiotensin receptor neprilysin inhibitor,” J. Clin. Pharmacol., vol. 56, no. 1, pp. 78–86, 2016, doi: 10.1002/jcph.571.
[10] P. J. B. Sunil S Jambhekak, “Pharmacokinetics,” Basic Pharmacokinet., no. Iv, 2016, doi: 10.1016/B978-0-12-801076-1.00019-8.
[11] O. Olafuyi, N. Parekh, J. Wright, and J. Koenig, “Inter-ethnic differences in pharmacokinetics—is there more that unites than divides?,” Pharmacol. Res. Perspect., vol. 9, no. 6, pp. 1–24, 2021, doi: 10.1002/prp2.890.
[12] D. A. Smith, K. Beaumont, T. S. Maurer, and L. Di, “Volume of Distribution in Drug Design,” J. Med. Chem., vol. 58, no. 15, pp. 5691–5698, 2015, doi: 10.1021/acs.jmedchem.5b00201.
[13] T. Wilson, R. R. Abrams, B. David, and D. B. Abrams, Area Under the Curve (AUC). 2013. doi: 10.1007/978-1-4419-1005-9.
[14] I. Zucker and B. J. Prendergast, “Sex differences in pharmacokinetics predict adverse drug reactions in women,” Biol. Sex Differ., vol. 11, no. 1, pp. 1–14, 2020, doi: 10.1186/s13293-020-00308-5.
[15] S. Ayalasomayajula et al., “Assessment of Drug–Drug Interaction Potential Between Atorvastatin and LCZ696, A Novel Angiotensin Receptor Neprilysin Inhibitor, in Healthy Chinese Male Subjects,” Eur. J. Drug Metab. Pharmacokinet., vol. 42, no. 2, pp. 309–318, 2017, doi: 10.1007/s13318-016-0349-y.
[16] H. ling Hsiao et al., “Pharmacokinetic drug-drug interaction assessment between LCZ696, an angiotensin receptor neprilysin inhibitor, and hydrochlorothiazide, amlodipine, or carvedilol,” Clin. Pharmacol. Drug Dev., vol. 4, no. 6, pp. 407–417, 2015, doi: 10.1002/cpdd.183.
[17] S. P. Ayalasomayajula et al., “Effect of renal function on the pharmacokinetics of LCZ696 (sacubitril/valsartan), an angiotensin receptor neprilysin inhibitor,” Eur. J. Clin. Pharmacol., vol. 72, no. 9, pp. 1065–1073, 2016, doi: 10.1007/s00228-016-2072-7.
[18] Y. Feng, Y. Yin, R. Deng, and H. Li, “Renal safety and efficacy of angiotensin receptor-neprilysin inhibitor: A meta-analysis of randomized controlled trials,” J. Clin. Pharm. Ther., vol. 45, no. 6, pp. 1235–1243, 2020, doi: 10.1111/jcpt.13243.
[19] R. Ogawa, J. M. Stachnik, and H. Echizen, “Clinical pharmacokinetics of drugs in patients with heart failure: An update (part 1, drugs administered intravenously),” Clin. Pharmacokinet., vol. 52, no. 3, pp. 169–185, 2013, doi: 10.1007/s40262-012-0029-2.
[20] S. P. Murphy, N. E. Ibrahim, and J. L. Januzzi, “Heart Failure with Reduced Ejection Fraction: A Review,” JAMA - J. Am. Med. Assoc., vol. 324, no. 5, pp. 488–504, 2020, doi: 10.1001/jama.2020.10262.
[21] Z. Kobalava et al., “Pharmacodynamic and Pharmacokinetic Profiles of Sacubitril/Valsartan (LCZ696) in Patients with Heart Failure and Reduced Ejection Fraction,” Cardiovasc. Ther., vol. 34, no. 4, pp. 191–198, 2016, doi: 10.1111/1755-5922.12183.
[22] A. A. Mangoni and E. A. Jarmuzewska, “The influence of heart failure on the pharmacokinetics of cardiovascular and non-cardiovascular drugs: a critical appraisal of the evidence,” Br. J. Clin. Pharmacol., vol. 85, no. 1, pp. 20–36, 2019, doi: 10.1111/bcp.13760.
[23] M. N. Khan et al., “Safety and tolerability of Sacubitril/Valsartan in heart failure patient with reduced ejection fraction,” BMC Cardiovasc. Disord., vol. 23, no. 1, pp. 1–7, 2023, doi: 10.1186/s12872-023-03070-9.
[24] M. Bialer, T. Shekh-Ahmad, T. L. Braun, and M. B. Halvorsen, “Comparative steady-state pharmacokinetic evaluation of immediate-release topiramate and USL255, a once-daily extended-release topiramate formulation,” Epilepsia, vol. 54, no. 8, pp. 1444–1452, 2013, doi: 10.1111/epi.12225.