Human Pharmacokinetic Data For Pentamidine

A pharmacokinetic study that allows estimates of the amount of pentamidine needed in both therapy and prophylactic trials using the Respirgard II device has been conducted in eight patients with diffuse alveolar infiltrates undergoing fiberoptic bronchoscopy for suspected PCP [14]. Bronchoalveolar lavage (BAL) sediment and supernatant concentrations of pentamidine were compared 18-24hr after administration of 4mg/kg IV (n = 3) and aerosolized (n = 5) pentamidine isethionate to different groups of patients. An aerosol containing 300 mg pentamidine isethionate in 6 mL distilled water was inhaled for 35-40 minutes. In patients with diffuse alveolar infiltrates, significantly higher concentrations of aerosolized pentamidine reached the airspaces than did the intravenous form of the drug. The BAL pentamidine concentrations in sediment were 9.34 ± 1.74ng/mL after IV administrations vs. 705 ± 242ng/mL after aerosol (mean ± SEM, p < 0.05). Serum pentamidine levels were low or undetectable after aerosolization. The large variation in BAL levels after aerosol but not intravenous administration suggests that the variability is due to aerosol deposition and not to BAL technique. Levels remain high; in the first patient to receive 12 monthly 300-mg treatments, a repeated BAL 31 days after the last treatment revealed 1,462 ng/mL in the sediment (B. Montgomery, unpublished data). Nevertheless, BAL cannot be used to provide an absolute alveolar concentration, because the total amount of alveolar fluid in the lungs cannot be determined. In addition, BAL fluid is contaminated by fluid in the airways. Conte and colleagues [17] conducted a similar study and also noted these limitations.

Despite the information about the pharmacokinetics of aerosolized pentamidine, how the drug is cleared from the lung is unknown. Some systemic absorption occurs and, therefore, this suggests the possibility of long-term systemic toxicity [14,17,18]. Furthermore, the moiety on pentamidine that causes a long pulmonary half-life has not been determined. Elucidation of this moiety may lead to development of novel long-lasting aerosol hybrid agents for other lung diseases. Studies of serial pentamidine levels in bronchial epithelial lining fluid after aerosol administration have shown that drug levels decreased rapidly within 2 weeks and were followed by a slow elimination rate [19].

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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