keywords: RP-HPLC, chloramphenicol, metformin, interactions, human plasma
Metformin is mostly prescribed with chloramphenicol in the treatment of diabetic mellitus with gastroenteritis and possible infections. However, the effect of this drug on the pharmacokinetic profile of metformin is yet to be established. The study was aimed at investigating the influence of chloramphenicol when co-administered with metformin on healthy volunteers. It is a one-way single-dose cross-over study in two phases. The subjects acted as their control, and each phase was preceded by an overnight fast. In phase one, metformin was administered to all the volunteers, while in phase two metformin was co-administered with 500 mg chloramphenicol. Plasma glucose levels were determined using the standard glucose oxidase method. Blood samples were collected at 0 - 8.0 and 24 h post-drug administration and stored at – 4 ˚C before analysis. Plasma samples were acidified with 0.5 ml of HCl and deproteinized with acetonitrile and centrifuged, the supernatant was washed with dichloromethane and injected into the HPLC system. Separation was achieved within 10 min on a Poroshell 120 EC-C18 (4.6mm x 50 mm 2.7 Microns) column with an isocratic mobile phase consisting 0f 0.03M dibasic ammonium phosphate (pH 7) and acetonitrile(10:90) % v/v) at a flow rate of 0.8 ml/min at a detection wavelength of 236 nm, and at ambient temperature. The samples were analyzed for metformin using a reversed phase. The results obtained from the study indicated pharmacokinetic changes though not statistically significant (P > 0.05), decreased in the (Cmax) and AUC0- 8 of metformin from 1,880.25± 0.45 to 1,710.35±0.4 ng/ml, 6,770.21±0.52 to 5,563.71±0.80 ng/ml/hr respectively and also decrease in the renal clearance by 38 %. The renal clearance of metformin was reduced in a time-dependent manner in the presence of chloramphenicol. This may be concluded that a combination of metformin with chloramphenicol may be clinically safe.