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.
Ball
B D
BD
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, University of Colorado Health Sciences Center, Denver.
Hill
M R
MR
Brenner
M
M
Sanks
R
R
Szefler
S J
SJ
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