Estimation of fetal risk from aerosolized pentamidine in pregnant healthcare workers.
Inhaled pentamidine is used to treat Pneumocystis carinii pneumonia. Its potential effects on DNA have raised concerns about its safety for pregnant healthcare workers. We used a pharmacokinetic approach to estimate the fetal risks, based on the published data of pentamidine renal clearance and of urinary pentamidine concentrations in healthcare workers exposed to aerosolized pentamidine. The maximum pentamidine doses (intravenous equivalent) that healthcare workers were exposed to were calculated to be 9.8 micrograms/kg/d and 1.7 microgram/kg/d at the two different institutions reported. In parallel, based on animal data, we derived the intravenous-equivalent reference doses for embryolethality and for teratogenicity, the doses that can be viewed as tentative safe exposure levels. These analyses reveal that the exposure levels of a healthcare worker to aerosolized pentamidine are estimated to be in the vicinity of the teratogenic reference dose (4 micrograms/kg/d) and greater than the embryolethal reference dose (0.08 microgram/kg/d). Further improvement of the pentamidine administration technique and of environmental management in hospitals is warranted.
Ito
S
S
Department of Pediatrics, Hospital for Sick Children, Toronto, Canada.
Koren
G
G
D000336:Aerosols; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006282:Health Personnel; D006801:Humans; D016273:Occupational Exposure / Q000009:adverse effects* / Q000706:statistics & numerical data; D010419:Pentamidine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D011247:Pregnancy; D012307:Risk Factors; D012449:Safety
D000336:Aerosols; D010419:Pentamidine