Research progress of pharmacokinetic evaluation methods on inhalable formulations

doi:10.12092/j.issn.1009-2501.2019.05.018

Abstract

Abstract:

Inhalable formulations have attracted increasing attentions due to the superiority in both local and systemic therapy. Thorough evaluation system is related to the quality of formulations, but the reported papers concerning inhalable formulations mainly focused on the evaluation of physicochemical properties. Pharmacokinetic evaluation is relatively ignored and the evaluation system is unsound. This paper reviews the pharmacokinetic evaluation methods in recent years, including the pharmacokinetic studies in animals, enzymes and cells, to further provide information for the establishment and improvement of pharmacokinetic evaluation system.

Key words: pulmonary delivery system, inhalable formulation, pharmacokinetic evaluation

CLC Number:

R969.1

KONG Ying, LI Ning, LU Yang, ZHAO Di, REN Chang, XING Han, CHEN Xijing. Research progress of pharmacokinetic evaluation methods on inhalable formulations[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(5): 595-600.

References

［1］Nakamura A, Nakajima M, Yamanaka H, et al. Expression of UGT1A and UGT2B mRNA in human normal tissues and various cell lines［J］. Drug Metab Dispos, 2008, 36(8): 1461-1464.
［2］Kuehl PJ, Grimes MJ, Dubose D, et al. Inhalation delivery of topotecan is superior to intravenous exposure for suppressing lung cancer in a preclinical model ［J］. Drug Deliv, 2018, 25(1): 1127-1136.
［3］Kell SA, Kachura MA, Renn A, et al. Preclinical development of the TLR9 agonist DV281 as an inhaled aerosolized immunotherapeutic for lung cancer: Pharmacological profile in mice, non-human primates, and human primary cells ［J］. Int Immunopharmacol, 2019, 66: 296-308.
［4］朱晓婕, 孔颖, 刘琦, 等. 叶酸靶向多西紫杉醇纳米肺吸入粉雾剂的制备及评价［J］. 中国临床药理学与治疗学, 2017, 22(5): 495-500.
［5］He J, Zhang G, Zhang Q, et al. Evaluation of inhaled recombinant human insulin dry powders: pharmacokinetics, pharmacodynamics and 14-day inhalation ［J］. J Pharm Pharmacol, 2019, 71(2): 176-184.
［6］Boger E, Friden M. Physiologically based pharmacokinetic/pharmacodynamic modeling accurately predicts the better bronchodilatory effect of inhaled versus oral salbutamol dosage forms ［J］. J Aerosol Med Pulm Drug Deliv, 2019, 32(1): 1-12.
［7］Patel B, Rashid J, Gupta N, et al. Low-mlecular-weight heparin-coated and montelukast-filled inhalable particles: a dual-drug delivery system for combination therapy in asthma ［J］. J Pharm Sci, 2017, 106(4): 1124-1135.
［8］Gaspar MC, Gregoire N, Sousa JJ, et al. Pulmonary pharmacokinetics of levofloxacin in rats after aerosolization of immediate-release chitosan or sustained-release PLGA microspheres［J］. Eur J Pharm Sci, 2016, 93: 184-191.
［9］Suzuki H, Ueno K, Mizumoto T, et al. Self-micellizing solid dispersion of cyclosporine A for pulmonary delivery: Physicochemical, pharmacokinetic and safety assessments ［J］. Eur J Pharm Sci, 2017, 96: 107-114.
［10］Okuda T, Morishita M, Mizutani K, et al. Development of spray-freeze-dried siRNA/PEI powder for inhalation with high aerosol performance and strong pulmonary gene silencing activity ［J］. J Control Release, 2018, 279: 99-113.
［11］Guilleminault L, Azzopardi N, Arnoult C, et al. Fate of inhaled monoclonal antibodies after the deposition of aerosolized particles in the respiratory system ［J］. J Control Release, 2014, 196: 344-354.
［12］Rashid J, Alobaida A, Al-Hilal TA, et al. Repurposing rosiglitazone, a PPAR-γ agonist and oral antidiabetic, as an inhaled formulation, for the treatment of PAH ［J］. J Control Release, 2018, 523(4): 234-244.
［13］Huang Y, Huang Z, Zhang X, et al. Chitosan-based binary dry powder inhaler carrier with nanometer roughness for improving in vitro and in vivo aerosolization performance ［J］. Drug Deliv Transl Re, 2018, 8(5): 1274-1288.
［14］Cuvelier B, Eloy P, Loira-Pastoriza C, et al. Minimal amounts of dipalmitoylphosphatidylcholine improve aerosol performance of spray-dried temocillin powders for inhalation ［J］. Int J Pharm, 2015, 495(2): 981-990.
［15］Geyer A, Lorenzer C, Gehrig S, et al. Fluorescence- and computed tomography for assessing the biodistribution of siRNA after intratracheal application in mice ［J］. Int J Pharm, 2017, 525(2): 359-366.
［16］Shen YB, Du Z, Tang C, et al. Formulation of insulin-loaded N-trimethyl chitosan microparticles with improved efficacy for inhalation by supercritical fluid assisted atomization ［J］. Int J Pharm, 2016, 505(1-2): 223-233.
［17］Scherlieb R, Mnckedieck M, Young K, et al. First in vivo evaluation of particulate nasal dry powder vaccine formulations containing ovalbumin in mice ［J］. Int J Pharm, 2015, 479(2): 408-415.
［18］Wang Q, Mi G, Hickey D, et al. Azithromycin-loaded respirable microparticles for targeted pulmonary delivery for the treatment of pneumonia ［J］. Biomaterials, 2018, 160: 107-123.
［19］Liao Q, Yip L, Chow MYT, et al. Porous and highly dispersible voriconazole dry powders produced by spray freeze drying for pulmonary delivery with efficient lung deposition ［J］. Int J Pharm, 2019, 560: 144-154.
［20］Hu Y, Li M, Zhang M, et al. Inhalation treatment of idiopathic pulmonary fibrosis with curcumin large porous microparticles ［J］. Int J Pharm, 2018, 551(1/2): 212-222.
［21］Fu TT, Zhao Y, Yang FF, et al. Ciclesonide and budesonide suspensions for nebulization delivery: An in vivo inhalation biopharmaceutics investigation ［J］. Int J Pharm, 2018, 549(1/2): 21-30.
［22］Eriksson J, Sjogren E, Thorn H, et al. Pulmonary absorption-estimation of effective pulmonary permeability and tissue retention of ten drugs using an ex vivo rat model and computational analysis ［J］. Eur J Pharm Biopharm, 2018, 124: 1-12.
［23］Gupta N, Al-Saikhan FI, Patel B, et al. Fasudil and SOD packaged in peptide-studded-liposomes: Properties, pharmacokinetics and ex-vivo targeting to isolated perfused rat lungs ［J］. Int J Pharm, 2015, 488(1-2): 33-43.
［24］Lu Phuong N, Dang Khoa N, Inthavong K, et al. Particle and inhalation exposure in human and monkey computational airway models ［J］. Inhal Toxicol, 2019: 1-13.
［25］Chen X, Huang W, Wong BC, et al. Liposomes prolong the therapeutic effect of anti-asthmatic medication via pulmonary delivery ［J］. Int J Nanomedicine, 2012, 7: 1139-1148.
［26］Hukkanen J, Pelkonen O, Hakkola J, et al. Expression and regulation of xenobiotic-metabolizing cytochrome P450 (CYP) enzymes in human lung ［J］. Crit Rev Toxicol, 2002, 32(5): 391-411.
［27］Ding X, Kaminsky LS. Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts ［J］. Annu Rev Pharmacol Toxicol, 2003, 43(1): 149-173.
［28］Dellinger RW, Fang JL, Chen G, et al. Importance of UDP-glucuronosyltransferase 1A10 (UGT1A10) in the detoxification of polycyclic aromatic hydrocarbons: decreased glucuronidative activity of the UGT1A10139Lys isoform ［J］. Drug Metab Dispos, 2006, 34(6): 943-949.
［29］Wei Z, Wanqing L, Federico I, et al. Searching for tissue-specific expression pattern-linked nucleotides of UGT1A isoforms ［J］. PLoS One, 2007, 2(4): e396.
［30］Shan L, Yang S, Zhang G, et al. Comparison of the inhibitory potential of bavachalcone and corylin against UDP-Glucuronosyltransferases ［J］. Evid Based Complement Alternat Med, 2014, 2014: 958937.
［31］Yilmaz Y, Williams G, Walles M, et al. Comparison of rat and human pulmonary metabolism using precision-cut lung slices (PCLS) ［J］. Drug Metab Lett, 2018.
［32］Zhu X, Kong Y, Liu Q, et al. Inhalable dry powder prepared from folic acid-conjugated docetaxel liposomes alters pharmacodynamic and pharmacokinetic properties relevant to lung cancer chemotherapy ［J］. Pulm Pharmacol Ther, 2019, 55:50-61.
［33］Patel B, Rashid J, Ahsan F. Aerosolizable modified-release particles of montelukast improve retention and availability of the drug in the lungs ［J］. Eur J Pharm Sci, 2017, 96: 560-570.
［34］Alimbetov D, Askarova S, Umbayev B, et al. Pharmacological targeting of cell cycle, apoptotic and cell adhesion signaling pathways implicated in chemoresistance of cancer cells ［J］. Int J Mol Sci, 2018, 19(6): 1690.
［35］Elgohary MM, Helmy MW, Abdelfattah EA, et al. Targeting sialic acid residues on lung cancer cells by inhalable boronic acid-decorated albumin nanocomposites for combined chemo/herbal therapy ［J］. J Control Release, 2018, 285: 230-243.
［36］Rosière R, Woensel MV, Mathieu V, et al. Development and evaluation of well-tolerated and tumor-penetrating polymeric micelle-based dry powders for inhaled anti-cancer chemotherapy ［J］. Int J Pharm, 2016, 501(1/2): 148-159.
［37］Jyoti K, Kaur K, Pandey RS, et al. Inhalable nanostructured lipid particles of 9-bromo-noscapine, a tubulin-binding cytotoxic agent: in vitro and in vivo studies ［J］. J Colloid Interf Sci, 2015, 445: 219-230.
［38］Foster KA, Avery ML, Yazdanian M, et al. Characterization of the Calu-3 cell line as a tool to screen pulmonary drug delivery ［J］. Int J Pharm, 2000, 208(1): 1-11.
［39］Xin OH, Daniela T, Young PM. Pharmaceutical applications of the Calu-3 lung epithelia cell line ［J］. Expert Opin Drug Deliv, 2013, 10(9): 1287-1302.
［40］Suzuki EY, Amaro MI, de Almeida GS, et al. Development of a new formulation of roflumilast for pulmonary drug delivery to treat inflammatory lung conditions ［J］. Int J Pharm, 2018, 550(1/2): 89-99.
［41］Salar-Behzadi S, Wu S, Mercuri A, et al. Effect of the pulmonary deposition and in vitro permeability on the prediction of plasma levels of inhaled budesonide formulation ［J］. Int J Pharm, 2017, 532(1): 337-344.
［42］Rigo LA, Carvalho-Wodarz CS, Pohlmann AR, et al. Nanoencapsulation of a glucocorticoid improves barrier function and anti-inflammatory effect on monolayers of pulmonary epithelial cell lines ［J］. Eur J Pharm Biopharm, 2017, 119: 1-10.
［43］Patel B, Gupta N, Ahsan F. Particle engineering to enhance or lessen particle uptake by alveolar macrophages and to influence the therapeutic outcome ［J］. Eur J Pharm Biopharm, 2015, 89: 163-174.
［44］陆亚媛, 赵娣, 李宁, 等. 缓释型肺吸入制剂的研究进展［J］. 药学研究, 2018, 37(8): 469-472,481.
［45］van Rijt SH, Bolukbas DA, Argyo C, et al. Applicability of avidin protein coated mesoporous silica nanoparticles as drug carriers in the lung ［J］. Nanoscale, 2016, 8(15): 8058-8069.
［46］Rashid J, Patel B, Nozik-Grayck E, et al. Inhaled sildenafil as an alternative to oral sildenafil in the treatment of pulmonary arterial hypertension (PAH) ［J］. J Control Release, 2017, 250: 96-106.

[1]	LIU Lu, SHI Yufei, HE Qingfeng, XU Fengyan, WANG Kun, CAI Weimin, XIANG Xiaoqiang. Application of population modeling analysis to evaluate the impact of gene polymorphism on drug PK/PD [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(11): 1275-1282.
[2]	LI Xuejing, JIANG Jinping, LI Sining, WAN Linfei, ZHOU Xiangxiang, YANG Lian, LAN Ke. A bioequivalence study of generic and brand clozapine in schizophrenic patients [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(10): 1121-1130.
[3]	WANG Fei, HANG Yongfu, WANG Wei. Influence of argumented renal clearance on teicoplannin serum concentrations in critical ill patients [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(9): 1043-1048.
[4]	HUANG Zhiwei, LI Yi, XU Xiaoyong, ZHANG Lei, SHEN Yifeng, LI Huafang. Comparison of calculation results of five population pharmacokinetic analysis tools [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(5): 525-535.
[5]	LI Mengxue, HE Jie, YU Xiaxia, HU Linlin, SHAO Hua. Research progress in population pharmacokinetics of rituximab [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(4): 468-474.
[6]	YAN Qiangyong, XIANG Daxiong, ZHU Ronghua, YANG Lingfeng, YANG Xiding, LI Jingjing, FAN Xiao, LIU Sai, XIONG Shoujun, FANG Pingfei. Bioequivalence study of cinacalcet hydrochloride tablets in healthy Chinese volunteers [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(2): 171-177.
[7]	YE Hongbo, SONG Yangyang, XUE Ling, RUI Jianzhong. Meropenem population pharmacokinetic model for the Chinese elderly established by model-based META analysis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(9): 984-990.
[8]	DU Wenpeng, AO Jiangen, TAO Yi, WU Guansheng, HE Jiake. Study on the factors affecting the steady-state blood concentration of tacrolimus in patients with autoimmune diseases [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(6): 645-651.
[9]	LIAN Jinfang, LIU Yiwei, LIN Cuihong, HUANG Pinfang, LIN Rongfang. Comparison of prediction accuracy between warfarin PPK/PD model and multiple regression dose models [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(3): 267-273.
[10]	WU Juan, WANG Zhiqiang, ZHOU Renpeng, YANG Jingjing, QIN Huiling, ZHANG Qian, LU Chao, HU Wei. Bioequivalence trial of fasting oral sorafenib tosylate tablets in healthy Chinese subjects [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(3): 281-286.
[11]	HU Yin, YANG Dandan, XU Yichao, SHAO Rong, RUAN Zourong, JIANG Bo, CHEN Jinliang, LOU Honggang. Application of artificial neural network model in bioequivalence study of candesartan cilexetil tablets [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(1): 63-69.
[12]	LIU Chang, DENG Kunhong, HUANG Jie, YANG Shuang, YANG Xiaoyan, XIANG Yuxia, HUANG Lu, ZHANG Zeyu, LIANG Wenzhong, LAN Jing, YANG Guoping. Bioequivalence of moxifloxacin hydrochloride tablets in healthy Chinese subjects [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(12): 1393-1399.
[13]	HAN Guijuan, JIANG Ji, OUYANG Weiwei, LUO Hong, ZHANG Xiaojun, WANG Minghua. Absorption and excretion of CT-707 in healthy male subjects studied by radioisotope tracer method [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(12): 1407-1412.
[14]	LI Na, HAN Hongcan, WANG Jun. General considerations for bioequivalence studies with pharmacokinetic methods for anti-schizophrenic drugs [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(12): 1419-1425.
[15]	ZHANG Miao, LIU Qian, YAO Xueting, LIU Dongyang. Exploration of early food effect study of innovative drugs based on physiologically-based pharmacokinetic absorption model [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(12): 1426-1429.