6 results on '"Robert M. Fielding"'
Search Results
2. [Untitled]
- Author
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Thomas J. Walsh, Robert M. Fielding, Richard Hiles, Ihor Bekersky, Garry Boswell, and Donald N. Buell
- Subjects
Pharmacology ,Liposome ,business.industry ,Organic Chemistry ,Pharmaceutical Science ,Dosage form ,Pharmacokinetics ,Amphotericin B ,Toxicity ,Molecular Medicine ,Toxicokinetics ,Medicine ,Distribution (pharmacology) ,Pharmacology (medical) ,business ,Drug carrier ,Biotechnology ,medicine.drug - Abstract
Purpose. Amphotericin B in small, unilamellar liposomes (AmBisome) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures, the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated.
- Published
- 2000
3. [Untitled]
- Author
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Donald N. Buell, Robert M. Fielding, Thomas J. Walsh, Richard Hiles, Ihor Bekersky, and Garry Boswell
- Subjects
Pharmacology ,Liposome ,business.industry ,Organic Chemistry ,technology, industry, and agriculture ,Pharmaceutical Science ,bacterial infections and mycoses ,Beagle ,Therapeutic index ,Pharmacokinetics ,Amphotericin B ,medicine ,Molecular Medicine ,Distribution (pharmacology) ,Toxicokinetics ,Pharmacology (medical) ,Liposomal amphotericin ,business ,Biotechnology ,medicine.drug - Abstract
Purpose. Amphotericin B (AmB) in small, unilamellar liposomes (AmBisome ®) has an improved therapeutic index, and altered pharmacokinetics. The repeat-dose safety and toxicokinetic profiles of AmBisome were studied at clinically relevant doses.
- Published
- 1999
4. [Untitled]
- Author
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Robert M. Fielding, Lotus Moon-Mcdermott, and Ramilla O. Lewis
- Subjects
Pharmacology ,Liposome ,Organic Chemistry ,Pharmaceutical Science ,Mononuclear phagocyte system ,Biology ,Dosage form ,Pharmacokinetics ,Amikacin ,medicine ,Molecular Medicine ,Distribution (pharmacology) ,Pharmacology (medical) ,Drug carrier ,Biotechnology ,Antibacterial agent ,medicine.drug - Abstract
Purpose. Amikacin in small unilamellar liposomes (MiKasome®) has prolonged plasma residence (half-life > 24hr) and sustained efficacy in Gram-negative infection models. Since low-clearance liposomes may be subject to a lower rate of phagocytic uptake, we hypothesized this formulation may enhance amikacin distribution to tissues outside the mononuclear phagocyte system.
- Published
- 1998
5. [Untitled]
- Author
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Laurence H. Wang, Robert M. Fielding, Philip C. Smith, and Luke S. S. Guo
- Subjects
medicine.drug_class ,animal diseases ,Antibiotics ,Pharmaceutical Science ,Spleen ,Pharmacology ,Nephrotoxicity ,Pharmacokinetics ,Amphotericin B ,parasitic diseases ,medicine ,Pharmacology (medical) ,Dosing ,Tissue distribution ,urogenital system ,Chemistry ,Organic Chemistry ,technology, industry, and agriculture ,bacterial infections and mycoses ,medicine.anatomical_structure ,Toxicity ,Immunology ,Molecular Medicine ,Biotechnology ,medicine.drug - Abstract
The pharmacokinetic profiles of amphotericin B (AmB) after administration of Amphocil®, an AmB/cholesteryl sulfate colloidal dispersion (ABCD) and the micellar AmB/deoxycholate (Fungizone®) were compared after repeated dosing in rats. After administration of ABCD and Fungizone at an equal AmB dose (1 mg/kg), AmB concentrations in plasma and most tissues were lower for the ABCD dose, especially in the kidneys where reduced drug concentration correlated with reduced nephrotoxicity. In contrast, AmB concentrations in the liver were substantially higher when ABCD was administered; however, without an accompanying increase in hepato-toxicity. Daily administration of ABCD for 14 days did not lead to AmB accumulation in plasma; while a slight accumulation was observed after multiple administration of Fungizone. AmB was eliminated more slowly from the plasma and various tissues and urinary and fecal recoveries of AmB were reduced after ABCD administration. These results suggest that ABCD may be stored in tissues in a form that is less toxic and is eliminated from the systemic circulation by a different mechanism than the free and protein-bound AmB in plasma. AmB accumulation in the spleen was observed when higher doses of ABCD (5 mg/kg) were administered, which could be due to saturation of hepatic uptake of AmB. Comparison of spleen concentrations of AmB between ABCD and Fungizone® at 5 mg/kg AmB doses was not possible because of Fungizone's toxicity in rats. In all other organs, AmB concentrations reached or approached a steady state within two weeks of dosing with ABCD. Urinary and fecal clearances of AmB were not different between ABCD and Fungizone administration. In summary, the distribution and elimination characteristics of AmB in rats were substantially altered when it was administered as ABCD in comparison to Fungizone. Nephrotoxicity of AmB in rats was reduced after administration of ABCD apparently because of the altered tissue distribution pattern. Thus, ABCD (Amphocil®) may be a clinically beneficial formulation of AmB in patients with systemic fungal infections.
- Published
- 1995
6. [Untitled]
- Author
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Robert M. Abra and Robert M. Fielding
- Subjects
Pharmacology ,Liposome ,Lung ,Chemistry ,medicine.drug_class ,Organic Chemistry ,Terbutaline ,Pharmaceutical Science ,Dosage form ,Pulmonary Absorption ,medicine.anatomical_structure ,Pharmacokinetics ,In vivo ,Anesthesia ,Bronchodilator ,medicine ,Molecular Medicine ,Pharmacology (medical) ,Biotechnology ,medicine.drug - Abstract
Maximum duration of bronchodilator efficacy in inhaled liposome-based formulations depends on optimizing the in vivo release rate of the encapsulated bronchodilator. We investigated the effect of several formulation variables on the pulmonary residence time of 3H-terbutaline sulfate liposomes administered intratracheally in guinea pigs, using an improved method enabling the measurement of pulmonary drug absorption for extended periods of time in conscious animals. Half-lives of liposome-encapsulated 3H-terbutaline disappearance from the lungs and airways after instillation ranged from 1.4 to 18 hr and were markedly affected by liposome size, cholesterol content, and phospholipid composition. This study demonstrates that liposomes can significantly prolong the residence time of bronchodilators in the lungs and that precise control over the pulmonary residence time of encapsulated bronchodilators can be achieved by controlling formulation variables.
- Published
- 1992
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