Absorption pulmonary

The kinetics of clearance of chromium salts from the lung suggest that systemic absorption is a rapid process that may be complete within 1 h after a single intratracheal dose (Bract and van Dura 1983). Subsequent clearance of chromium from the lung can be described as a sum of exponential terms with half-lives of the order of days up to 1 month (Bract and van Dura 1983 Weber 1983). Pulmonary clearance of chromium is not dose dependent within a reasonable dose range (Bract and van Dura 1983 Weber 1983). 

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No studies were located regarding absorption in humans and animals after inhalation exposure to methyl parathion. However, it can be concluded that pulmonary absorption occurred in humans as evidenced by... 

GIT, is considered to be lost from the absorption site, as is metabolic clearance and sequestration in various cell types and membranes (72,14). It is clear from Scheme I that the relative rates of the various processes will define the bioavailable fraction of the dose and understanding those factors which control pulmonary absorption kinetics is obviously the key to enhancing bioavailability via the lung. In a recent book (75) the molecular dependence of lung binding and metabolism was considered alongside the parallel processes of absorption, clearance and dissolution in the lung (14). Some key features of this work will be repeated as it relates to the systemic delivery of polypeptides. 

During occupational exposure, respiratory absorption of soluble and insoluble nickel compounds is the major route of entry, with gastrointestinal absorption secondary (WHO 1991). Inhalation exposure studies of nickel in humans and test animals show that nickel localizes in the lungs, with much lower levels in liver and kidneys (USPHS 1993). About half the inhaled nickel is deposited on bronchial mucosa and swept upward in mucous to be swallowed about 25% of the inhaled nickel is deposited in the pulmonary parenchyma (NAS 1975). The relative amount of inhaled nickel absorbed from the pulmonary tract is dependent on the chemical and physical properties of the nickel compound (USEPA 1986). Pulmonary absorption into the blood is greatest for nickel carbonyl vapor about half the inhaled amount is absorbed (USEPA 1980). Nickel in particulate matter is absorbed from the pulmonary tract to a lesser degree than nickel carbonyl however, smaller particles are absorbed more readily than larger ones (USEPA 1980). Large nickel particles (>2 pm in diameter) are deposited in the upper respiratory tract smaller particles tend to enter the lower respiratory tract. In humans, 35% of the inhaled nickel is absorbed into the blood from the respiratory tract the remainder is either swallowed or expectorated. Soluble nickel compounds... 

Gas uptake studies with rats showed that pulmonary absorption of HCFC-141b into the systemic circulation is a first-order process (Loizou and Anders 1993 Loizou et al. 1996). 

The pulmonary absorption and metabolism of an opioid tetrapeptide was investigated in the IPL and in rats in vivo by Tronde and co-workers [68, 140], The lung metabolism, compared after airway and vascular delivery, was consistently showed to be higher after airway delivery indicating some first-pass... 

Freiwald M, Valotis A, Kirschbaum A, McClellan M, Murdter T, Fritz P, Friedel G, Thomas M, Hogger P (2005) Monitoring the initial pulmonary absorption of two different beclomethasone dipropionate aerosols employing a human lung reperfusion model. Respir Res 24 6-21. 

Lombry C, Edwards DA, Preat V, Vanbever R (2004) Alveolar macrophages are a primary barrier to pulmonary absorption of macromolecules. Am J Physiol 286 L1002-1008. 

Sakagami M (2006) In vivo, in vitro and ex vivo models to assess pulmonary absorption and disposition of inhaled therapeutics for systemic delivery. Adv Drug Deliv Rev 58 1030-1060. 

Schanker LS, Hemberger JA (1983) Relation between molecular weight and pulmonary absorption rate of lipid-insoluble compounds in neonatal and adult rats. Biochem Pharmacol 32 2599-2601. 

Schmekel B, Borgstrom L, Wollmer P (1991) Difference in pulmonary absorption of inhaled terbutaline in healthy smokers and non-smokers. Thorax 46 225-228. 

Tronde A, Norden B, Marchner H, Wendel AK, Lennernas H, Bengtsson UH (2003) Pulmonary absorption rate and bioavailability of drugs in vivo in rats structure-absorption relationships and physicochemical profiling of inhaled drugs. JPharmSci 92 1216-1233. 

Wall DA (1995) Pulmonary absorption of peptides and proteins. Drug Debv 2 1-20. 

Elbert KJ, Schafer UF, Schafers HJ, Kim KJ, Lee VHL, Lehr CM (1999) Mono-layers of human alveolar epithelial cells in primary culture for pulmonary absorption and transport studies. Pharm Res 16(5) 601-608... 

Chloroform absorption depends on the concentration in inhaled air, the duration of exposure, the blood/air partition coefficient, the solubility in various tissues, and the state of physical activity which influences the ventilation rate and cardiac output. Pulmonary absorption of chloroform is also influenced by total body weight and total fat content, with uptake and storage in adipose tissue increasing with excess body weight and obesity. 

In relation to systemic absorption of drugs, absorption in the lung can be described as the passage of a series of barriers by the drug in order to enter the systemic circulation. It is important to realize that physiological conditions in the lung differ widely from site to site. Major physiological factors that affect pulmonary absorption are [10] ... 

For an efficient pulmonary absorption process, the alveolar membrane seems to be an optimal absorption site for a number of reasons. 

Many studies have been carried out regarding the absorption of peptides and proteins after pulmonary drug dehvery. The perspectives of a non-parenteral route of administration for larger proteins led to studies on the pulmonary absorption of proteins of different size. To date, over 30 different proteins have been evaluated with regard to absorption rate and... 

Although there are many cases of human overexposure to carbon tetrachloride vapor, there are few quantitative studies of pulmonary absorption of carbon tetrachloride in humans. Based on the difference in carbon tetrachloride concentration in inhaled and exhaled air, absorption across the lung was estimated to be about 60% in humans (Lehmann and Schmidt-Kehl 1936). In animals, monkeys exposed to 50 ppm absorbed an average of 30.4% of the total amount of carbon tetrachloride inhaled, at an average absorption rate of 0.022 mg carbon tetrachloride/kg/minute (McCollister et al. 1951). The concentration of carbon tetrachloride in the blood increased steadily, but did not reach a steady-state within 344 minutes of exposure. 

Pulmonary absorption of volatile anesthetics across the alveolar-capillary barrier is very rapid because of the relatively high lipid-water partition coefficients and small molecular radii of such agents. The driving force for diffusion is a combination of the blood-air partition coefficient (which is a measure of the capacity of blood to dissolve drug) and the difference in partial pressure between the alveoli and the arterial and venous blood. Agents with high blood-air partition coefficients require more drug to be dissolved in the blood for equilibrium to be reached. 

Yamamoto, A., S. Okumura, Y. Fukuda, M. Fukui, K. Takahashi, and S. Muranishi, Improvement of the pulmonary absorption of (Asul,7)-eel calcitonin by various absorption enhancers and their pulmonary toxicity in rats. J Pharm Sci, 1997. 86(10) 1144-7. 

Liposomes were formed from 1,2-dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Choi) and the effect of liposomal entrapment on pulmonary absorption of insulin was related to oligomerization of insulin (Liu et al. 1993). Instillation of both dimeric and hexameric insulin produced equivalent duration of hypoglycemic response. However, the initial response from the hexameric form was slightly slower than that from dimeric insulin, probably due to lower permeability across alveolar epithelium of the hexameric form caused by larger molecular size. The intratracheal administration of liposomal insulin enhanced pulmonary absorption and resulted in an absolute bioavailability of 30.3%. Nevertheless, a similar extent of absorption and hypoglycemic effects was obtained from a physical mixture of insulin and blank liposomes and from liposomal insulin. This suggests a specific interaction of the phospholipid with the surfactant layer or even with the alveolar membrane. 

Not only will the charge of a lipid and the composition of lipids affect the delivery of biomacromolecules, but the size of the liposome may alter the transport. Mixtures of insulin with three different diameter (1.98 pm, 0.4 pm, and 0.1 pm) neutral liposomes (DPPC Choi) resulted in similar overall hypoglycemic effects to insulin alone. Contrary to this finding is the fact that pulmonary absorption of liposomal [3H] terbutaline, a small molecule, has been reported to be dependent on both composition and size of the liposomes used (Abra et al. 1990). Differences in the absorption mechanism may be the explanation for this contradictory evidence further studies are needed to clarify this and other uncertainties about the uptake mechanism of macromolecules (Patton 1996). 

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