Understanding variability in response to gliclazide

Type 2 diabetes has become one of the most common human diseases. The safety and efficacy of antidiabetic medicines is an important part of diabetes management in the community. This thesis investigates a number of factors that may potentially cause variability in response to the antidiabetic drug gliclazide. This information will help to improve the use of these medicines in diabetic patients. Patients have free access to, and commonly take, complementary medicines for a variety of reasons. Many take these in conjunction with conventional drugs without clear evidence of safety or risk of herb—drug interactions. St John’s wort is one of the most widely used herbal medicines in Western societies. The aim of the first clinical study in this thesis was to investigate potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between St John’s wort and gliclazide in healthy subjects with different cytochrome P450 2C9 (CYP2C9) and CYP2C19 genotypes