Theoretical decrease in systemic availability with decrease in input rate at steady-state for first-pass drugs
✍ Scribed by John G. Wagner; Edward J. Antal; Alfred T. Elvin; William R. Gillespie; Evelyn A. Pratt; Kenneth S. Albert
- Publisher
- John Wiley and Sons
- Year
- 1985
- Tongue
- English
- Weight
- 118 KB
- Volume
- 6
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
KEY WORDS Systemic availability Michaelis-Menten kinetics Sinusoidal perfusion model THEORETICAL Equation (1) is the general ~n e ' -~ which relates all important variables of the sinusoidal perfusion model for the steady-state situation,
where v is the velocity of metabolism of the drug in the liver (masshime), Q is the liver blood flow (volume/time), K*, is the Michaelis constant, C,, is the outlet (venous concentration) of unchanged drug being metabolized, Ci is the inlet (arterial) concentration of drug and V*, is the maximal velocity of metabolism (masshime), V*, and K*, have different numerical values than the corresponding values, V , and K,, of the venous equilibration ('well-stirred') modeL6
At steady-state v = R = constant rate of input of the drug (masshime). Also, CJCi is the systemic* availability, F, of the drug.' Replacing v by R and *We are assuming that only hepatic metabolism occurs.