title: Penetration of corticosteroids into the lung: evidence for a difference between methylprednisolone and prednisolone.
abstract: Little is known about the penetration of corticosteroids, such as methylprednisolone and prednisolone, into the lung, despite their common use in the treatment of inflammatory lung diseases. To compare methylprednisolone and prednisolone concentrations in the bronchoalveolar space, we administered these two corticosteroids in a randomized, crossover fashion to 17 adult rabbits. A loading dose was administered and was followed by a continuous infusion for 180 minutes to achieve steady-state plasma concentrations between 200 to 2000 ng/ml. Serial plasma samples were obtained during the infusions. Bronchoalveolar lavages (BAL) were performed at 180 minutes with sterile saline. Plasma and BAL fluid (BALF) were assayed for methylprednisolone and prednisolone concentration by high-performance liquid chromatography. Corticosteroid concentrations were normalized to urea concentrations in plasma and BALF. Generally, BALF corticosteroid concentration increased as plasma concentration increased. At plasma concentrations greater than 800 ng/ml, BALF methylprednisolone concentrations increased exponentially, whereas the increase for prednisolone remained linear. BALF methylprednisolone was five times as high as that of prednisolone when plasma corticosteroid concentration was in the 2000 ng/ml range. With this continuous infusion technique, methylprednisolone has a higher degree of bronchoalveolar penetration than prednisolone, and these differences are greater at higher plasma concentrations.
authors.affiliation: Ira J. and Jacqueline Neimark Laboratory of Clinical Pharmacology in Pediatrics, Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
authors.forename: P
authors.initials: P
authors.lastname: Vichyanond
authors.forename: C G
authors.initials: CG
authors.lastname: Irvin
authors.forename: G L
authors.initials: GL
authors.lastname: Larsen
authors.forename: S J
authors.initials: SJ
authors.lastname: Szefler
authors.forename: M R
authors.initials: MR
authors.lastname: Hill
mesh_terms: D000305:Adrenal Cortex Hormones / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism*; D008775:Methylprednisolone / Q000493:pharmacokinetics*; D009994:Osmolar Concentration; D011239:Prednisolone / Q000493:pharmacokinetics*; D011817:Rabbits; D014508:Urea / Q000097:blood / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D014508:Urea; D011239:Prednisolone; D008775:Methylprednisolone