In vivo comparisons of constitutive cytochrome P450 3A activity assessed by alprazolam, triazolam, and midazolam

Abstract

Despite alprazolam, midazolam, and triazolam having markedly different pharmacokinetic characteristics, statistically significant correlations were present between the oral and systemic clearances of the 3 drugs, consistent with a major involvement of CYP3A in their metabolism and elimination. However, the magnitude of the coefficients of determination ( r s ) was such to suggest that an in vivo probe approach, even with the use of valid phenotypic trait values, will be unable to accurately and reliably predict the pharmacokinetic behavior of another CYP3A substrate, as determined by the enzyme's constitutive activity.