Effect of low-dose troleandomycin on glucocorticoid pharmacokinetics and airway hyperresponsiveness in severely asthmatic children.
Fifteen hospitalized asthmatic children (8 to 18 years old) completed a 2-week randomized, parallel, double-blind placebo-controlled comparison of combination methylprednisolone and placebo troleandomycin, prednisone and troleandomycin (P-TAO) or methylprednisolone-TAO (MPn-TAO). Troleandomycin (250 mg once daily or every other day) and glucocorticoid doses were reduced by a standard protocol. Symptom scores, blood chemistries, pulmonary function tests, airway response to methacholine, and glucocorticoid pharmacokinetics were compared. In each group, a steroid dose reduction of 50% was achieved without a deterioration in symptom scores. Methacholine response was unchanged in all five on methylprednisolone alone, but decreased 3-fold to 30-fold in two of five on combination P-TAO, and four of five on combination MPn-TAO. Troleandomycin decreased MPn clearance by an average of 62% but did not alter prednisolone clearance. Low-dose TAO combined with MPn has a significant effect on methylprednisolone clearance in children, an effect equivalent to that reported with higher dose TAO (1000 mg/d) therapy. In addition, this preliminary study suggests that TAO may decrease bronchial hyperresponsiveness to methacholine in severely asthmatic children.
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, University of Colorado Health Sciences Center, Denver.
B D
BD
Ball
M R
MR
Hill
M
M
Brenner
R
R
Sanks
S J
SJ
Szefler
D000293:Adolescent; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D002648:Child; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000493:pharmacokinetics*; D006801:Humans; D016210:Methacholine Chloride; D008688:Methacholine Compounds; D008775:Methylprednisolone / Q000009:adverse effects / Q000627:therapeutic use; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D012129:Respiratory Function Tests; D012130:Respiratory Hypersensitivity / Q000188:drug therapy*; D014217:Troleandomycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
D005938:Glucocorticoids; D008688:Methacholine Compounds; D016210:Methacholine Chloride; D011239:Prednisolone; D014217:Troleandomycin; D008775:Methylprednisolone