Details

Autor(en) / Beteiligte

• Browne, Thomas R.
• Szabo, George K.
• Walsh, Carol T.
• Schumacher, Gerald E.
• Evans, James E.
• Evans, Barbara A.

Titel

New Pharmacokinetic Methods II: Determination of the Presence or Absence of Product Inhibition in Drugs with Nonlinear Pharmacokinetics

Ist Teil von

• Journal of clinical pharmacology, 1990-07, Vol.30 (7), p.578-584

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

1990

Quelle

MEDLINE

Beschreibungen/Notizen

• We show that for drugs metabolized by one enzyme the slope of a plot of serum concentration (C) versus 1/clearance (CL) is linear with a value of 1/Vmax in the presence of substrate saturation and may be linear (rarely) or curved (usually) with a slope always greater than 1/Vmax in the presence of substrate saturation and product inhibition (competitive, noncompetitive, or uncompetitive) when the serum concentration of product varies with the serum concentration of substrate. Serum concentration, CL, and Vmax were determined for a group of six subjects receiving phenytoin monotherapy using three approaches. With each approach: 1) a plot C versus 1/CL was linear (r ≥ 0.738, P < .01); 2) the slope of this regression line did not differ significantly (P > .30) from 1/Vmax. We conclude: 1) our method is a simple and useful method for determination of mechanism of a drug's nonlinear pharmacokinetics (substrate saturation versus substrate saturation and product inhibition), 2) phenytoin has nonlinear pharmacokinetics due to substrate saturation only in man.