No abstract

It is shown that the absorption of phenylbutazone, naproxen, and chlorthiazide is governed by a dose limiting mechanism. This dose dependency may be explained by a saturation absorption process mathematically obeying Michaelis-Menten type kinetics. Observed dose relationships for tetracycline, fenclozic acid and related compounds, phenytoin, and possibly digoxin and digitoxin may be explained if a saturable process in absorption is postulated. This behavior may be produced by insolubility of the drug compound, a limited "window of absorption" in the gastrointestinal tract, or a capacity limited absorption because of the carrier or the transport mechanism involved. The need for suitably designed dose response studies with new drug compounds is discussed.

DZM showed minimal clinical toxicity and significant efficacy despite lower plasma concentrations than predicted by pharmacokinetics. This trial establishes the suitability of the n-of-1 design to investigational antiepileptic drug trials.

No abstract

SUMMARY. Thalidomide is now widely used to treat chronic graft-versus-host disease, but its use is associated with non-teratogenic side effects such as peripheral neuropathy. To examine the value of monitoring plasma concentrations of the drug in such patients, we have developed a high-performance liquid chromatographic (HPLC) assay. The method uses O·5 mL plasma, is linear to 10 mg/L and had a detection limit of O·2 mg/L. Thalidomide in plasma specimens was unstable at physiological pH but could be stabilized for several weeks by simple acidification. We describe a protocol for monitoring patients treated with thalidomide which permits convenient transportation and storage of specimens and report, provisionally, that plasma concentrations in the range 1-7 mg/L are therapeutically effective in chronic graft-versus-host disease without adverse side effects.