Pentamidine large dose

Currently, pentamidine in the form of aerosol is used for the prophylaxis of PCP with apparent success [163-166]. Initially no renal side effects were described with its use. However, two reports of acute renal dysfunction raised the possibility of a systemic absorption of aerosolized pentamidine [167, 168]. One of the patients received a previous large dose of TMP-SMZ and the other appears to have had concomitant volume depletion caused by severe diarrhea while an elevation of serum creatinine occurred. We have been unable to find additional reports of renal toxicity associated with aerosol pentamidine administration[169]. Likewise, no renal side effects were reported with the use of aerosolized pentamidine for the prophylaxis of PCP in patients who received bone marrow, renal or hepatic transplants [165, 166]. Although the use of aerosolized pentamidine may be associated with renal dysfunction, this seems much less frequent compared to the parenteral administration of this drug. 

Early experimental studies of pentamidine renal toxicity in animals were limited to few sheep, goats [170] and rabbits [171] given rather large doses of pentamidine (up to 40 mg/kg). The results of these studies, although indicating some degree of renal toxicity, are difficult to interpret because of the small number of animals employed, the large doses of pentamidine used, and the absence of controls or detailed renal function studies. 

Despite their availability, neither dry powder nor metered-dose inhalers have been used to deliver aerosolized pentamidine. The use of metered-dose inhalers may be problematic because these devices are better suited for frequent delivery of small doses rather than intermittent delivery of the large doses that have been therapeutically successful in prophylaxis of PCP. Dry powder devices may produce an increased incidence of cough due to airway deposition. 

Inadequate experience has been obtained to determine the incidence of the infrequent adverse reactions that will be associated with aerosolized pentamidine therapy for acute PCP. In case reports, bronchial bleeding has been reported with high-dose therapy in one center [43]. This was associated with an invasive procedure and has not been seen in the large prospective treatment trial. Case reports of hypoglycemia, rash, and conjunctivitis have also been reported [44,45]. The conjunctivitis is not unexpected it would be the direct consequence of... 

Monthly aerosolized pentamidine has been utilized as prophylactic therapy against Pneumocystis carinii pneumonia in high-risk patients with HIV infection. While effective, this therapy fails in a certain percentage of patients. In the large clinical trials defining the clinical efficacy of this mode of therapy, the dose-response curve was not determined. Whether patients who failed prophylaxis did so because of inadequate deposition of aerosolized pentamidine or other unknown factors remained uncertain. Figure 13 represents summary data from a smdy in 58 patients receiving directly supervised monthly therapy in... 

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