Dexamethasone: pharmacokinetics in neurological patients.

A high performance liquid chromatographic assay has been used to measure the time courses of plasma dexamethasone concentrations in patients with various neurological disorders being treated with this steroid. The pharmacokinetics of the drug in these circumstances differed from the kinetics in healthy volunteers. In particular whole body clearances were higher, causing a substantially impaired mean oral bioavailability of the drug with considerable interindividual variation in bioavailability. The clearance of dexamethasone was increased by concurrent phenytoin therapy, and dexamethasone and phenytoin are often given together in neurosurgical practice. The previously unrecognized bioavailability limitation of oral dexamethasone may explain individual instances of apparent steroid-resistant neurological disease, and suggests the desirability of monitoring plasma dexamethasone levels when using the steroid therapeutically. Some preliminary evidence has been obtained suggesting that it may be possible to avoid adrenal suppression from long-term high-dosage dexamethasone therapy, if plasma dexamethasone levels can be allowed to fall to zero between consecutive dexamethasone doses.