13c-erythromycin Breath Test to Determine Drug Dosages

Period of Performance: 02/01/1994 - 07/31/1994

Unknown

Phase 1 SBIR

Recipient Firm

Metabolic Solutions, Inc.
Nashua, NH 03063
Principal Investigator

Abstract

The long term objective of this study is to develop a nonradioactive, noninvasive breath test to predict blood drug levels. We will develop a 13C breath test to measure cytochrome P450IIIA enzyme activity. Many drugs, such as cyclosporine, are metabolized by this p450 family. The catalytic activity of p450IIIA will be estimated from the rate at which a patient exhales 13CO2 after receiving an oral dose of [N,N-dimethyl-13C2]- erythromycin. In previous studies, Dr. Paul Watkins showed that an intravenous dose of radioactive 14C-erythromycin would be N-demethylated by P450IIIA enzymes. The production of breath 14CO2 correlated with P450IIIA levels and catalytic activity. Further research showed that the 14C- erythromycin breath test accurately predicts cyclosporine blood levels in patients receiving different dosages. The activity of P450IIIA varies ten fold in humans and may account for heterogeneity of cyclosporine dosing requirements. Knowledge of P450IIIA activity could predict a cyclosporine blood level for a given drug dosage. The clinician will utilize this information to prevent either potentially subtherapeutic or potentially toxic dosages of cyclosporine to be administered to patients. The correct dosage of cyclosporine could be achieved in a shorter hospital stay with this breath test compared to the current method of measuring blood levels.