Therapeutic management of diabetic patients frequently involves polypharmacy which is likely to provoke drug-drug interactions (DDIs). This may require appropriate monitoring and most common clinically relevant DDIs that occur with antidiabetic medications often leads to variations in therapeutic response. Due to the wide use of artesunate combination in the treatment of malaria in diabetic patients, drug interactions with gliclazide is a possibility. This study was aimed at determining the effect of artesunate on the pharmacokinetics of gliclazide in diabetic subjects. Six freshly diagnosed diabetics subjects participated in the study. Written informed consent was sought and obtained from the volunteers. The study is a one-way single dose cross-over study in two phases. Phase 1 of the study involved the administration of a single oral dose of 80 mg of gliclazide after an overnight fast. After a wash out period of one week, 80 mg gliclazide and 100 mg artesunate were co-administered. Serial blood samples were collected over a period of 24 h during each phase into an EDTA vacutainer. High Performance Liquid Chromatography method was used in the estimation of plasma glucose concentration; while the glucose oxidase peroxidase method was used in the estimation of plasma glucose concentration. Results showed changes in the pharmacokinetic parameters and blood glucose concentration were not significant (p>0.05). This shows that artesunate does not alter the pharmacokinetics and of gliclazide in diabetic patients after single oral dose administration; and hence can be co-administered without dose modification.

The study aims at investigating the effect of amodiaquine on the pharmacokinetic profile of gliclazide. It is a one-way single dose cross-over study in two phases. Six freshly diagnosed diabetic volunteers were used. The subjects acted as their own control, and each phase was preceded by an overnight fast. Phase 1 of the study involved the administration of a single oral dose of 80 mg of gliclazide after an overnight fast. After a wash out period of one week, 80 mg gliclazide and 300 mg amodiaquine were coadministered. Serial blood samples were collected over a period of 24 h during each phase into an Ethylenediaminetetraacetic acid (EDTA) vacutainer. After collection, blood samples were processed. A validated High Performance Liquid Chromatography (HPLC) method was used in the estimation of serum gliclazide concentration. Glucose oxidase peroxidase method was used in the estimation of blood glucose concentration. The pharmacokinetic parameters derived by a non-compartmental analysis with two periods (gliclazide alone and in combination with amodiaquine) were compared. The pharmacodynamics as measured by blood glucose concentration was also compared for the 2 phases of the study. Results showed that though amodiaquine affects the rate of absorption of gliclazide, it does not affect the bioavailability and overall disposition of gliclazide after a single oral dose. A lack of pharmacodynamic interactions between amodiaquine and gliclazide was also observed. Conclusively, amodiaquine and gliclazide can be concurrently administered together without fear of loss of activity.

Diabetic patients do have co-occurring diseases like malaria, especially in tropical regions. Hence, polypharmacy is sometimes unavoidable. Gliclazide is widely used in the treatment of non-insulin-dependent type 2 diabetes mellitus, while dihydro-artemisinin (DHA) is one of the most promising medications used in the treatment of malaria on account of its good efficacy and tolerability. The study evaluated the effect of DHA on the pharmacokinetics of gliclazide in diabetic patients. This is a single dose one-way, cross-over study in two periods, with each phase preceded by an overnight fast. Six subjects that passed inclusion criteria participated in the study. The volunteers acted as their control. Phase 1 of the study involved administering a single oral dose of 80 mg of gliclazide after an overnight fast. After a washout period of one week, 80 mg gliclazide and 120 mg DHA were co-administered. Serial blood samples were collected at time intervals throughout 24 h and processed. A validated HPLC method was used to estimate serum gliclazide concentration, while the glucose oxidase peroxidase method was used in the evaluation of blood glucose concentration. The Pharmacokinetic Software - PharmPK was used to generate the pharmacokinetic parameters. GraphPad Prism version 7.01 software for window was used for data analysis. Statistical differences observed in the pharmacokinetic profiles of gliclazide and blood glucose concentration were not significant. Single oral dose of gliclazide and dihydro-artemisinin had good safety and tolerability in diabetic subjects. Keywords: Diabetes mellitus, Dihydro-artemisinin, Drug Interactions, Gliclazide, Pharmacokinetics

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