RE: NONMEM and identification of drug-drug interactions

From: "Gibiansky, Ekaterina" <Katyag@mocr.oapi.com> Subject: RE: NONMEM and identification of drug-drug interactions Date: 17 Dec 1997 14:48:03 -0500 Gary, Recently I was involved in the population PK of cilostazol where we looked at drug-drug interactions. We screened all the concomitant medications used by more than 25 patients (5% of all the patients). Of 21 different drugs, diltiazem showed to increase cilostazol exposure [Gibiansky et al. Pharm. Res. 1997 14(11):515]. Retrospectively, it made sense: diltiazem was a CYP3A4 inhibitor. Cilostazol is metabolized via 3A4, and it was known that erythromycin increased cilostazol exposure. Initially, the idea was to look at frequently coadministered drugs, and separately to look at inhibitors and stimulators of certain isozymes grouped together. But for most of drugs we were not able to find that information. Katya Gibiansky Otsuka America Pharmaceuticals, Inc. 2440 Research Blvd, Rockville, MD 20850 USA E-mail: katyag@mocr.oapi.com Phone: (301)-527-4911 Fax: (301)-721-7511