Figure 2.
Final rifapentine pharmacokinetic-enzyme model. The number of transit compartments was estimated using the relationship kTR = (N + 1)/MTT. The ka was assumed to equal the kTR. Rifapentine autoinduction was modeled with an enzyme turnover model, in which the EFF of rifapentine concentration in the central compartment increased the kENZ, thereby increasing the ENZ. Rifapentine CL increased as a result of increased ENZ. The F increased (+) or decreased (−) as indicated. CL = clearance; CLm = metabolite clearance; EFF = effect; ENZ = enzyme pool; F = fraction of drug absorbed or relative availability; ka = absorption rate constant; kENZ = enzyme production rate; kTR = transit-rate constant; MTT = mean transit time; V = apparent volume of distribution; Vm = metabolite volume of distribution.