High dose aerosol pentamidine for secondaryPneumocystis carinii pneumonia prophylaxis in AIDS patients

Flamholc, Leo; Haidl, Sven; Westin, Elsebet; Borgdalen, Lena; Prellner, ThorbjÖRn

doi:10.1007/bf01710670

Cited by 3 publications

(1 citation statement)

References 14 publications

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“…2 ). In addition, pentamidine, when used as an aerosol, is selectively distributed to the lungs without systemic side effects, even at a comparatively high dose ( 19 ), and an important application of linezolid is the treatment of GPB-associated pulmonary infections ( 20 ). Their combination is expected to be designed as an aerosol to treat pulmonary infections.…”

Section: Discussionmentioning

confidence: 99%

When Combined with Pentamidine, Originally Ineffective Linezolid Becomes Active in Carbapenem-Resistant Enterobacteriaceae

et al. 2023

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Section: Discussionmentioning

confidence: 99%

When Combined with Pentamidine, Originally Ineffective Linezolid Becomes Active in Carbapenem-Resistant Enterobacteriaceae

et al. 2023

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Intrapulmonary and Systemic Pharmacokinetics of Aerosolized Pentamidine Used for Prophylaxis of Pneumocystis carinii Pneumonia in Patients Infected with the Human Immunodeficiency Virus

Conte

Golden

1995

The Journal of Clinical Pharma

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A study was conducted to determine the intrapulmonary and systemic pharmacokinetics of aerosolized pentamidine prophylaxis (APP) in patients infected with human immunodeficiency virus (HIV). 151 patients received high-dose (300 mg twice a month or 600 mg once a month) APP as part of a previously published clinical trial, and 29 additional patients received standard-dose (300 mg once a month) APP. Serial blood samples were obtained from the first cohort: 577 samples were obtained from 76 patients in the group given 600 mg once a month, and 554 blood samples were obtained from 75 patients in the group given 300 mg twice a month. In 9 of the 151 patients, bronchoscopy and tri-lobar (right upper, middle, and lower lobe) bronchoalveolar lavage (BAL) were performed 6 and 12 months after initiation of APP. Unilobar (right middle lobe) BAL was performed in the 29 patients infected with HIV who underwent bronchoscopy for diagnostic purposes. Pentamidine was measured using a chromatographic (HPLC) assay. The concentrations (mean +/- SD) of pentamidine in plasma in the groups given 300 mg twice a month and 600 mg once a month were 5.3 +/- 6.1 ng/mL and 8.8 +/- 9.6 ng/mL, respectively, and accumulation did not occur. The BAL supernatant and alveolar cell pentamidine concentrations were not significantly different in the 3 lobes and ranged from 16.5 +/- 7.7 ng/mL to 29.2 +/- 19.5 ng/mL and 1255 +/- 1142 ng/mg protein to 1572 +/- 1161 ng/mg protein in the group given 300 mg twice a month; and from 5.5 +/- 2.9 ng/mL to 9.4 +/- 7.7 ng/mL and 339 +/- 201 ng/mg protein to 571+/- 681 ng/mg protein in the group given 600 mg once a month. The intropulmonary concentrations of pentamidine at 6 and 12 months were not significantly different. In 18 of the 29 patients who received 1 to 7 prior monthly doses of standard APP, drug concentrations in BAL increased linearly (y = 2.05x) with the number of doses administered before bronchoscopy. These data indicate that intrapulmonary drug concentrations continue to increase for approximately 6 months after the initiation of APP, at which time steady state is achieved, and that administration of high dose APP is probably safe.

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Aerosolization of imipenem/cilastatin prevents pseudomonas-induced acute lung injury

Hashimoto

Wolfe

Guglielmo

et al. 1996

Journal of Antimicrobial Chemotherapy

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Aerosolization of imipenem/cilastatin was compared with continuous intravenous infusions of the antibiotic for pharmacokinetic/pharmacodynamic analysis. The concentrations of imipenim/cilastatin in bronchoalveolar lavage fluids (BAL) obtained from rats exposed to the aerosolized antibiotic were significantly greater than the concentrations in BAL in the rats that had received intravenous infusions of imipenem/cilastatin. The two methods of antibiotic delivery were compared for their effects on bacterial-induced lung injury in rats that had Pseudomonas aeruginosa instilled into their airspaces. The aerosolization of antibiotic was associated with significantly decreased bacterial-induced lung injury. The high concentrations of antibiotic in the airspaces secondary to aerosolization appears to kill bacteria more quickly and preserve lung epithelial and endothelial integrity better than systemic delivery of the same antibiotic.

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High dose aerosol pentamidine for secondaryPneumocystis carinii pneumonia prophylaxis in AIDS patients

Cited by 3 publications

References 14 publications

When Combined with Pentamidine, Originally Ineffective Linezolid Becomes Active in Carbapenem-Resistant Enterobacteriaceae

When Combined with Pentamidine, Originally Ineffective Linezolid Becomes Active in Carbapenem-Resistant Enterobacteriaceae

Intrapulmonary and Systemic Pharmacokinetics of Aerosolized Pentamidine Used for Prophylaxis of Pneumocystis carinii Pneumonia in Patients Infected with the Human Immunodeficiency Virus

Aerosolization of imipenem/cilastatin prevents pseudomonas-induced acute lung injury

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