13C-Erythromycin Breath Test to Determine Drug Dosages

We will develop a nonradioactive, noninvasive breath test to predict blood drug levels. We willdevelop a 13C breath test to measure cytochrome P450IIIA enzyme activity. Many drugs, such ascyclosporine, are metabolized by this p450 family. The catalytic activity of p450IIIA will be estimatedfrom the rate at which a patient exhales 13CO2 after receiving an oral dose of [N,N-dimethyl-13C2]-eryt-hromycin. In previous studies, we showed that an intravenous dose of radioactive 14C-erythromycinwould be N-demethylated by P450IIIA enzymes. The production of breath 14CO2 correlated withP450IIIA levels and catalytic activity. Further research showed that the 14C-erythromycin breath testaccurately predicts cyclosporine blood levels in patients receiving different dosages. The activity ofP450IIIA varies ten fold in humans and may account for heterogeneity of cyclosporine dosingrequirements. Knowledge of P450IIIA activity could predict a cyclosporine blood level for a given drugdosage. The clinician will utilize this information to prevent either potentially subtherapeutic orpotentially toxic dosages of cyclosporine to be administered to patients. The correct dosage ofcyclosporine could be achieved in a shorter hospital stay with this breath test compared to the currentmethod of measuring blood levels.