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Systems Pharmacolog...
Systems Pharmacology Approach for Prediction of Pulmonary and Systemic Pharmacokinetics and Receptor Occupancy of Inhaled Drugs
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- Boger, E. (author)
- AstraZeneca R&D, Dept Resp Inflammat & Autoimmun Innovat Med, Molndal, Sweden.;Univ Warwick, Sch Engn, Coventry, W Midlands, England.
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- Evans, N. (author)
- Univ Warwick, Sch Engn, Coventry, W Midlands, England.
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- Chappell, M. (author)
- Univ Warwick, Sch Engn, Coventry, W Midlands, England.
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- Lundqvist, A. (author)
- AstraZeneca R&D, Dept Resp Inflammat & Autoimmun Innovat Med, Molndal, Sweden.
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- Ewing, P. (author)
- AstraZeneca R&D, Dept Resp Inflammat & Autoimmun Innovat Med, Molndal, Sweden.
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- Wigenborg, A. (author)
- AstraZeneca R&D, Dept Resp Inflammat & Autoimmun Innovat Med, Molndal, Sweden.
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- Fridén, Markus (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,AstraZeneca R&D, Dept Resp Inflammat & Autoimmun Innovat Med, Molndal, Sweden.
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AstraZeneca R&D, Dept Resp Inflammat & Autoimmun Innovat Med, Molndal, Sweden;Univ Warwick, Sch Engn, Coventry, W Midlands, England. Univ Warwick, Sch Engn, Coventry, W Midlands, England. (creator_code:org_t)
- 2016-04-14
- 2016
- English.
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In: CPT. - : Wiley. - 2163-8306. ; 5:4, s. 201-210
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Abstract
Subject headings
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- Pulmonary drug disposition after inhalation is complex involving mechanisms, such as regional drug deposition, dissolution, and mucociliary clearance. This study aimed to develop a systems pharmacology approach to mechanistically describe lung disposition in rats and thereby provide an integrated understanding of the system. When drug-and formulation-specific properties for the poorly soluble drug fluticasone propionate were fed into the model, it proved predictive of the pharmacokinetics and receptor occupancy after intravenous administration and nose-only inhalation. As the model clearly distinguishes among drug-specific, formulation-specific, and system-specific properties, it was possible to identify key determinants of pulmonary selectivity of receptor occupancy of inhaled drugs: slow particle dissolution and slow drug-receptor dissociation. Hence, it enables assessment of factors for lung targeting, including molecular properties, formulation, as well as the physiology of the animal species, thereby providing a general framework for rational drug design and facilitated translation of lung targeting from animal to man.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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