Estimation of possible drug interactions that could be caused by montelukast on CYP2C8-cleared drugs

Values used for montelukast include: D = 10 mg; Fa = 0.62; ka = 0.008/min; fu = 0.01; Cmax = 603 ng/ml = 1.0 μM (Zhao et al., 1997); Ki = 0.0092 μM. The fraction of the affected drug metabolized by CYP2C8 is assumed to be unity in the expression. The estimate for Fa = 0.62 was made from the observation that clearance after intravenous administration was reported at 0.7 ml/min/kg (Cheng et al., 1996); hence, hepatic extraction is less than 5%, and oral bioavailability is 62%. The estimate for ka was made from the expression Tmax = (ln(ka/kel))/(kakel) in which kel was calculated from the reported t1/2 and Tmax values of 4.7 h and 3.5 h, respectively (Cheng et al., 1996).

In Vivo Inhibitor Concentration Available to the Enzyme

Equation Used to Estimate the in Vivo Inhibitor Concentration ([I]in vivo) Available to the Enzyme

Magnitude of Drug Interaction (Fold Increase in Exposure) Embedded Image
Systemic total Cmax [I]in vivo = Cmax 112
Systemic free Cmax [I]in vivo = fu · Cmax 2.1
Estimated total portal Cmax [I]in vivo = Cmax + ka · Fa · D/Qh 119
Estimated free portal Cmax
[I]in vivo = fu · (Cmax + ka · Fa · D/Qh)
  • AUC, area under the curve.