Pulmonary deposition of nebulised pentamidine isethionate: effect of nebuliser type, dose, and volume of fill.

Abstract

An estimate of the absolute pulmonary deposition of nebulised pentamidine isethionate was obtained in nine patients with AIDS. Two nebuliser systems were compared, System 22 Mizer (Medic-Aid) and Respirgard II (Marquest), with 50 and 150 mg doses of pentamidine in a 3 ml solution driven by an air flow of 6 l/min with the patient in the sitting position. The 50 mg pentamidine dose was repeated with a 6 ml fill with both devices. The nebuliser cloud was labelled with technetium-99m human serum albumin (Ventocol) and lung deposition was measured with a gamma camera. Of the two nebulisers studied, System 22 Mizer delivered more drug to the lungs as a whole and tpo each individual lung region, including the peripheral and upper zones. For the 50 mg dose the mean (SEM) total pulmonary deposition with the 3 and the 6 ml fill respectively was 2.63 (0.34) and 3.71 (0.41) mg for the System 22 Mizer and 1.37 (0.26) and 1.45 (0.18) mg for the Respirgard II. For the 150 mg dose the System 22 Mizer delivered 7.16 (1.02) mg and the Respirgard II 4.34 (0.57) mg. Increasing the volume of fill from 3 to 6 ml increased pulmonary deposition with System 22 Mizer, and this was related to a increase in nebuliser output. Neither pulmonary deposition nor nebuliser output was increased by using a 6 ml solution in the Respirgard II. Increasing the volume of fill prolonged the time required for nebulisation with both nebulisers. The System 22 Mizer produced more non-pulmonary (gastric and oropharyngeal) deposition of drug, more frequent local adverse effects (cough, burning in the throat, and a metallic taste), and small reductions in lung function, particularly with the 150 mg pentamidine dose. Thus nebulizer type, volume of fill, and nebuliser dose affect the pulmonary deposition of pentamidine. A 300 mg dose of pentamidine via a Respirgard II is generally recommended as providing effective prophylaxis; our results suggest that similar pulmonary deposition can be produced with System 22 Mizer and 150 mg pentamidine. A clinical trial would be needed to show whether this regimen provides similar prophylactic benefit.