Biliary elimination of ceftazidime

Abstract

When five normal subjects were given ceftazidime 2 g iv, antibiotic concentrations in aspirated duodenal fluid increased progressively during 4 h to a value of 21.2 +/- 9.2 mg/l (mean +/- S.E.M.); 0.05% of the dose given was recovered in duodenal fluid. The same dose was given to 12 patients with an external biliary drain. The mean peak ceftazidime concentration of 36.3 +/- 4.0 mg/l was reached in the collected bile during the second hour after administration. The 12-h biliary recovery was 0.21% of the dose. The respective ceftazidime concentrations in choledochal and gallbladder bile sampled peroperatively in ten patients 1 h after ceftazidime 2 g iv were 78.3 +/- 12.0 and 17.9 +/- 7.5 mg/l. These data compare favourably with the results achieved with other beta-lactam compounds.

Fate of aerosolized recombinant DNA-produced alpha 1-antitrypsin: use of the epithelial surface of the lower respiratory tract to administer proteins of therapeutic importance.

“…Comparison ofELF, lymph, blood, and urine rAAT levels demonstrated that the process was concentration dependent, with highest levels in ELF and in descending concentrations with 410-fold concentration differences in each consecutive compartment, respectively. Importantly (6,7), and studies with recombinant interferon-'y, interferon-a, and granulocytemonocyte colony-stimulating factor, erythropoietin, and interleukin 2 have necessitated subcutaneous, intramuscular, or intravenous routes of administration (1-5, 9, 10).…”

“…Comparison ofELF, lymph, blood, and urine rAAT levels demonstrated that the process was concentration dependent, with highest levels in ELF and in descending concentrations with 410-fold concentration differences in each consecutive compartment, respectively. Importantly (6,7), and studies with recombinant interferon-'y, interferon-a, and granulocytemonocyte colony-stimulating factor, erythropoietin, and interleukin 2 have necessitated subcutaneous, intramuscular, or intravenous routes of administration (1-5, 9, 10).As an alternative approach to administration ofrecombinant proteins (and proteins in general, independent of the source), the present study was designed to capitalize on the enormous surface area of the lung as a potential absorptive surface through which proteins of therapeutic importance could gain access to the interstitium of the lung and plasma while remaining intact. This concept is based on the knowledge that (i) droplets of 3-,um diameter inhaled as an aerosol have the potential to reach the alveolar surface (11-14); (ii) the epithelial surface of the human lower respiratory tract is very large, typically 140 m2 in adults (15); (iii) plasma proteins as large as 100 kDa are found in the epithelial lining fluid surface of the lung, suggesting that proteins can diffuse across the capillary endothelium, the alveolar interstitium, and the alveolar epithelium (16)(17)(18)(19); and (iv) although there are no quantitative data available relating to the measurement of autologous natural or recombinant proteins from lower respiratory tract epithelial lining fluid to plasma, it is known that when solutions of heterologous proteins are instilled in the trachea of experimental animals, the protein can be subsequently detected in the pulmonary interstitium and blood (20)(21)(22).…”

“…The development of recombinant DNA technologies has made available a variety of human proteins that have potential as therapeutic agents in the treatment of human disorders (1)(2)(3)(4)(5)(6)(7)(8). However, in contrast to the relative ease of production of recombinant molecules, one serious obstacle to their use is that as proteins they are susceptible to proteolysis in the gastrointestinal tract and are not absorbed through the skin, thus necessitating that they be administered by a subcutaneous, intramuscular, or intravenous route (1)(2)(3)(4)(5)(6)(7)(8).…”

“…However, in contrast to the relative ease of production of recombinant molecules, one serious obstacle to their use is that as proteins they are susceptible to proteolysis in the gastrointestinal tract and are not absorbed through the skin, thus necessitating that they be administered by a subcutaneous, intramuscular, or intravenous route (1)(2)(3)(4)(5)(6)(7)(8). This is not a problem for proteins used therapeutically only in acute situations such as tissue plasminogen activator (8), but it markedly complicates the use of recombinant proteins in the repetitive treatment of chronic disease.…”

“…This is not a problem for proteins used therapeutically only in acute situations such as tissue plasminogen activator (8), but it markedly complicates the use of recombinant proteins in the repetitive treatment of chronic disease. For example, recombinant growth hormone and insulin are routinely administered by the subcutaneous route (6,7), and studies with recombinant interferon-'y, interferon-a, and granulocytemonocyte colony-stimulating factor, erythropoietin, and interleukin 2 have necessitated subcutaneous, intramuscular, or intravenous routes of administration (1-5, 9, 10).…”