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Lung deposition of nebulised pentamidine in children
M J O'Doherty1, S H Thomas, D Gibb
1Department of Nuclear Medicine, United Medical School, St Thomas' Hospital, London, UK.
Insights
Children likely need lower nebulised pentamidine doses for effective Pneumocystis pneumonia prevention. Lung aerosol concentration was higher in children than adults, suggesting dose adjustments are needed.
Area of Science:
- Pediatric Pulmonology
- Pharmacokinetics
- Infectious Disease Prevention
Background:
- Nebulised pentamidine is a proven Pneumocystis pneumonia (PCP) prophylactic in adults with HIV/AIDS.
- Optimal dosing for pediatric PCP prevention via nebulised pentamidine remains undetermined.
- This study aimed to quantify pulmonary pentamidine deposition in children.
Purpose of the Study:
- To measure pentamidine deposition in the lungs of children receiving nebulised treatments.
- To correlate pentamidine deposition with pediatric patient age, ventilation patterns, and body size.
- To inform appropriate nebulised pentamidine dosing for pediatric PCP prophylaxis.
Main Methods:
- 12 children and 6 adults with HIV received nebulised pentamidine (50 mg/6 ml saline) via Respirgard II nebuliser.
- 99mTc-labeled albumin served as a marker for aerosol deposition, quantified by gamma camera imaging.
- Pulmonary deposition was assessed relative to nebuliser output and predicted total lung capacity.
Main Results:
- Absolute pentamidine deposition was independent of age, height, weight, or ventilation parameters.
- Percentage of nebuliser output deposited was similar across pediatric and adult groups (5.5-7.2%).
- Lung aerosol concentration was higher in children and teenagers due to smaller lung volumes, negatively correlating with height and weight.
Conclusions:
- Pediatric patients exhibit higher lung aerosol concentrations of pentamidine compared to adults.
- Lower nebuliser pentamidine doses are likely required in children for equivalent therapeutic lung concentrations.
- Findings support adjusted dosing strategies for nebulised pentamidine in pediatric PCP prevention.
Background:
Nebulised pentamidine is effective for preventing Pneumocystis carinii pneumonia in adults with acquired immunodeficiency syndrome. The nebuliser dose required to produce equivalent lung concentrations of pentamidine in children is unknown. This study was performed to measure pulmonary pentamidine deposition in children and to relate this to age, ventilation pattern, and body size.
Methods:
Nebulised pentamidine (50 mg in 6 ml saline) was administered to 12 children (including one with lymphocytic interstitial pneumonitis) and to six adults with human immunodeficiency virus infection using a Respirgard II nebuliser. Technetium-99m labeled colloidal human serum albumin was used as an indirect marker for pentamidine and deposition in the lungs was detected by a gamma camera.
Results:
Absolute deposition of pentamidine was not related to age, height, weight, spirometry, or ventilation characteristics. Deposition, as a mean (SD) percentage of nebuliser output, was similar in children aged 8-11 years (5.5(2.4)%), teenagers aged 12-15 years (7.2(2.2)%) and adults (7.1(2.6)%). Aerosol concentration within the lungs (% nebuliser output deposited/predicted total lung capacity) was therefore higher in children (1.9(1.5)%/1) and teenagers (1.9(0.7)%/1) than in adults (1.0(0.7%)/1), and was negatively correlated with height (r = -0.69) and weight (r = -0.50). Deposition of aerosol in the region of the large central airways was particularly marked in children. Small reductions in forced expiratory volume in one second and forced vital capacity after treatment did not differ significantly between adults and children and visual analogue scores of subjective adverse effects did not vary with age.
Conclusions:
These results suggest that children probably require lower nebuliser pentamidine doses to produce lung pentamidine concentrations equivalent to those found to be effective for preventing P carinii pneumonia in adults using the Respirgard II nebuliser.