THE PHARMACOKINETICS OF GLICLAZIDE AND CIPROFLOXACIN AFTER SINGLE AND JOINT ADMINISTRATION IN WISTAR MALE RATS MODEL WITH RENAL FAILURE

• Main Author: Kamilah Pratiwi, Gladdis
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/45693
• Institution: Institut Teknologi Bandung

Diabetic nephropathy is one of serious microvascular and macrovascular complications due to chronic hyperglycaemia. It causes renal dysfunction which could be worsened by urinary tract infection. Gliclazide is an oral antidiabetic medication recommended for patients with diabetic nephropathy, whereas ciprofloxacin is an antibiotic commonly used for urinary tract infection. The purpose of this study was to evaluate the effects of renal failure on the pharmacokinetics of gliclazide and ciprofloxacin, and possible pharmacokinetic interactions of these drugs when given in combination. Male Wistar rats were used in this current study and renal failure was induced using gentamycin. Gliclazide and ciprofloxacin were given in a single dose (0.033 and 0.103 mg/g BW), and multiple doses to the anesthetized rats. Blood samples were withdrawn from femoral artery before the drug administration and at the specified sampling point up to 24 h and 18 h for gliclazide and ciprofloxacin, respectively. Gliclazide and ciprofloxacin concentrations in plasma samples were determined using HPLC, then pharmacokinetic parameters were calculated and statistically analyzed. Pharmacokinetic parameters of gliclazide and ciprofloxacin in the renal failure rats were different compared to the normal rats from the previous study, particularly in absorption and elimination phases. AUC0-?of ciprofloxacin in the renal failure group increased from 3.46 ± 0.91 to 14.72 ± 0.73 ?g.hours/mL. Pharmacokinetics of gliclazide administered in combination with ciprofloxacin multiple doses showed significant differences in absorption, distribution and elimination phases. Furthermore, AUC0-?of gliclazide was also increased from 147.85±0.96 to 195.83±19.52 ?g.h/mL. In contrast, gliclazide did not significantly affect ciprofloxacin pharmacokinetics. Renal failure changed the pharmacokinetics of both drugs and multiple doses of ciprofloxacin altered the pharmacokinetics of gliclazide. The findings might suggest that blood glucose levels should be monitored when ciprofloxacin is given to the diabetic nephropaty patients using gliclazide.