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Distribution of pentamidine in patients with AIDS
H Donnelly1, E M Bernard, H Rothkotter
1Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Abstract:
We used a bioassay to measure pentamidine concentrations in autopsy specimens from 22 patients with AIDS. Patients received pentamidine isethionate (approximately 4 mg/kg per day) parenterally for Pneumocystis carinii pneumonia; one received monthly prophylaxis. We found that lung levels of 30 micrograms/g were achieved only after the fifth dose; tissue accumulation was usually greater in the liver, kidney, adrenal, and spleen than in the lung; detectable levels were present in some tissues as late as one year after the last dose; and low but detectable levels were present in the brain of six of 17 patients. Two patients had no detectable lung levels after two days of therapy; one had a level of 17.5 micrograms/g after four doses, and two had levels of 30 micrograms/g after five doses. A more rapid and effective method of delivery, such as aerosol, should achieve higher concentrations earlier. Because pentamidine persists in lung tissue over days to weeks, daily administration may not be necessary.
Insights
Pentamidine concentrations in AIDS patients show slow accumulation in lung tissue, with detectable levels persisting for up to a year. Alternative delivery methods like aerosol may be more effective for treating Pneumocystis pneumonia.
Area of Science:
- Pharmacology
- Infectious Diseases
- Clinical Medicine
Background:
- Pentamidine isethionate is a key treatment for Pneumocystis carinii pneumonia (PCP) in patients with Acquired Immunodeficiency Syndrome (AIDS).
- Understanding pentamidine pharmacokinetics, including tissue distribution and persistence, is crucial for optimizing treatment regimens.
Purpose of the Study:
- To quantify pentamidine concentrations in autopsy tissues from AIDS patients treated for PCP.
- To evaluate the relationship between dosage, duration of therapy, and pentamidine tissue levels.
- To assess the persistence of pentamidine in various tissues over time.
Main Methods:
- Bioassay analysis of pentamidine concentrations in autopsy specimens from 22 AIDS patients.
- Patients received parenteral pentamidine isethionate for PCP treatment or prophylaxis.
- Tissue samples analyzed included lung, liver, kidney, adrenal gland, spleen, and brain.
Main Results:
- Therapeutic lung concentrations (30 µg/g) were achieved after the fifth dose.
- Higher pentamidine accumulation was observed in liver, kidney, adrenal, and spleen compared to lung.
- Detectable pentamidine levels persisted in some tissues for up to one year post-treatment.
- Low levels were detected in the brain of 6 out of 17 patients.
Conclusions:
- Parenteral pentamidine administration leads to slow accumulation and prolonged persistence in tissues, including the lung.
- Alternative delivery methods, such as aerosolized pentamidine, could potentially achieve higher and earlier therapeutic concentrations.
- The long persistence of pentamidine in lung tissue suggests that daily administration may not be necessary, potentially allowing for less frequent dosing schedules.