Measuring the parent drug alone can understate an exposure change when a metabolite is also active. A phase 1 study of an investigational IV rifabutin formulation illustrates the distinction.
The researchers studied rifabutin and its active metabolite, 25-O-desacetyl rifabutin, after BV100 administration in healthy participants. With itraconazole, rifabutin area under the curve increased about 1.3- to 1.7-fold, depending on the measure. The authors reported a disproportionate increase in exposure to the metabolite and roughly a twofold increase in total active-moiety exposure.
A parent-drug ratio and a combined exposure estimate describe different endpoints. In a toxicology report, identify which analyte was measured and which summary is being cited. The ratios describe the studied formulation and conditions. They do not establish the size of a clinical effect in an individual.
Phase 1 interaction studies of investigational IV rifabutin formulation BV100 (full text) ยท DOI