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K T Miller

Publications and source records attributed to K T Miller.

5 recordsLinked to original sources
PubMed1989

Pharmacokinetics of methotrexate in the cerebrospinal fluid after intracerebroventricular administration in patients with meningeal carcinomatosis and altered cerebrospinal fluid flow dynamics.

Pharmacokinetic parameters of the distribution and elimination of intracerebroventricularly administered methotrexate (MTX) were evaluated in three patients with meningeal carcinomatosis. Abnormal cerebrospinal fluid (CSF) flow dynamics, which were not otherwise clinically evident, were diagnosed by 111In-diethylenetriaminepentaacetate radionuclide imaging. Alterations in CSF flow resulted in large changes in MTX distribution. Reduced cortical convexity (type III), spinal subarachnoid (type II), or ventricular (type I) CSF flow resulted in a prolongation of the single-pass mean residence time of MTX in the peripheral compartment by as much as eightfold and a reduction in intercompartmental clearance by 94-99%. Leptomeningeal carcinomatosis can affect both CSF MTX distribution and elimination, each to a different extent, within the same patient. Total MTX clearance from the CSF was reduced by 79-93% in the patients studied. A two-compartment pharmacokinetic model, with elimination occurring from the peripheral compartment, gave values for the distribution rate constant from the central to the peripheral compartment (k12), which decreased with the extent of CSF flow abnormality. However, the elimination rate constant from the peripheral compartment (k20) was reduced to an extent apparently independent of CSF flow abnormality (percentage reduction in k12 and k20, respectively: type III, 18 and 66; type II, 67 and 86; type I, 78 and 48). Inadequate distribution and locally high concentrations of MTX within the CSF may contribute to therapeutic failure and neurotoxicity. Monitoring of MTX levels in the CSF may be deceiving when samples are drawn from the site of injection, since the distribution kinetics are altered by abnormal CSF flow dynamics.

Adult↗
PubMedDate not supplied

Drug delivery into the arterial wall: a time-course study with use of a lipophilic dye.

PURPOSE: One potential approach to the prevention of restenosis after angioplasty is to deliver antiproliferative agents directly to the angioplasty site. The purpose of this study was to determine the time course of drug penetration into the media of the balloon-dilated artery. MATERIALS AND METHODS: Balloon angioplasty of the left and right iliac arteries was performed once for 1 minute in each of five rabbits. A double-balloon catheter was then positioned at the site of angioplasty, and the fluorescent dye PKH26 (molecular weight, 961) was delivered under pressure to simulate drug delivery. Afterward, the arteries were removed and dye penetration into the media was measured on frozen cross sections by epifluorescence microscopy. RESULTS: Delivery of the dye was performed for periods ranging from 5 to 50 minutes at a mean pressure of 189 mm Hg. The depth of dye penetration (D, micrometers) was directly related to dye perfusion time (T, minutes) (D = 0.348T + 11.958, r = 0.496, P < .01). This equation predicts complete medial dye penetration in 81 minutes assuming an average intima-media thickness (40 microns). CONCLUSION: This study demonstrates that PKH26 can be delivered to the media of the dilated artery. However, the time required to obtain complete penetration may limit the utility of this double-balloon catheter approach to drug delivery.

Angioplasty, Balloon↗