Effects of Gatifloxacin on Serum Glucose Concentration in Normal and Diabetic Rats

Abstract

To clarify the mechanisms of gatifloxacin (GFLX)-induced hypoglycemia and hyperglycemia, the effect of GFLX on serum glucose levels was investigated in normal and diabetic rats. Rats received an intravenous injection of GFLX and their arterial blood was sampled periodically. Diabetic rats were produced by the intraperitoneal injection of streptozotocin and nicotinamide. In normal rats, the serum glucose concentration was decreased by GFLX at 25 and 50 mg/kg, while it was elevated 0.25 h after the injection of 100 mg/kg of GFLX. Serum immunoreactive insulin (IRI) levels increased as the dose of GFLX increased. The serum epinephrine concentration rose rapidly after the injection of GFLX at 50 and 100 mg/kg. In diabetic rats, the serum glucose concentration was actually increased by GFLX at 50 mg/kg. The baseline concentration of IRI was lower and the degree of the elevation caused by GFLX was smaller in diabetic rats. Both diabetic and control rats showed an increase in the serum epinephrine concentration after the injection of 50 mg/kg of GFLX. In conclusion, GFLXinduced secretion of insulin and epinephrine would contribute to the abnormalities in glucose homeostasis. The response of serum glucose to GFLX may differ between diabetic and normal rats due to the alteration of insulin secretion.Key words gatifloxacin; hypoglycemia; hyperglycemia; insulin; epinephrine; diabetes mellitus © 2006 Pharmaceutical Society of Japan * To whom correspondence should be addressed. e-mail: yasuhara.mpha@tmd.ac.jp IRI, and Epinephrine in Diabetic RatsTo induce diabetes mellitus in rats, streptozotocin (65 mg/kg) was injected intraperitoneally into overnight-fasted rats 15 min after an intraperitoneal injection of nicotinamide (110 mg/kg). 18,19) Seven days later, rats with an overnight-fasted serum glucose level above 160 mg/dl were taken for the experiment. The equivalent volume of 0.05 mol/l citrate buffer (vehicle) and nicotinamide were injected as a control (non-diabetic rats).GFLX was injected through the cannula into diabetic and non-diabetic rats at 50 mg/kg, and the equivalent volume of normal saline was injected into other diabetic rats (diabetic control rats). Blood samples were obtained at 0, 0.25, 0.5, 1, 2, 4, 6, and 8 h to determine serum concentrations of glucose and GFLX. Serum IRI concentration was determined at 0, 0.5, 1, 2, 4, and 6 h.In another set of rats, same procedure was performed, and blood samples were obtained at 0, 0.25, 1, and 4 h to determine serum epinephrine concentration.Analytical Methods The serum concentration of glucose was determined by the glucose oxidase method using a Glucose CII-test Wako (Wako Pure Chemical Industries). The serum concentration of IRI was determined by enzyme immunoassay using a Glazyme Insulin-EIA TEST (Wako Pure Chemical Industries).The serum concentration of epinephrine was determined by HPLC with pre-column fluorescence derivatization, using a slightly modified method of Mitsui et al. 20) Briefly, 400 ml of serum was mixed with 200 ml of 2.0 mol/l perchloric acid an...

The insulinotropic effect of fluoroquinolones

“…However, it must be noted that the hypoglycemias mostly occur at the beginning of a fluoroquinolone therapy [38], whereas after several days of therapy, when different intracellular accumulation may be more important, hyperglycemias are more frequent. While hyperglycemias may involve extrapancreatic effects [39], our observation that the fluoroquinolones at 100 µM were ineffective to stimulate insulin secretion in the presence of a basal glucose concentration leads to the provocative question why these compounds are hypoglycemic at all. Intriguingly, diabetes is a strong risk factor, independently of a sulfonylurea or insulin therapy [40] In conclusion, it seems that the K ATP channel-blocking effect is a necessary but not a sufficient condition for the hypoglycemic side effect of the fluoroquinolones.…”

Clinicopathological Aspect of Dysglycemia in Naive and Diabetic Rats induced by the Fluoroquinolone Antibacterial Gatifloxacin

“…Tomita et al [19] reported that GFLX induced insulin oversecretion in the short-term, and decreased insulin productivity or increased insulin disintegration in the long-term using the insulin-secreting cell line HIT-T15. Based on the in vivo studies, Ishiwata et al [10] reported that serum glucose concentrations decreased and increased in normal and streptozotocin-induced diabetic rats, respectively, given a single intravenous injection of GFLX at 50 mg/kg, with elevations in both serum insulin and epinephrine (adrenaline) concentrations. However, few reports have dealt with the clinicopathological process of hypoglycemia or hyperglycemia induced by GFLX after repeated oral administration using the identical animals.…”

An acute experimental study to evaluate the effect of gatifloxacin on blood sugar levels in diabetic and non-diabetic rabbits

“…25 mg/kg, as a single oral dose, for the study. 9 Oral suspension of the drug was made in 2% gum acacia and dose was adjusted to a volume of 2-5 ml daily for albino rabbits, which was administered with the help of a feeding catheter. Study medication was administered to the fasting animals after drawing samples for baseline values.…”

“…9 Reports also mention that, in patients with type 2 diabetes mellitus, gatifloxacin caused an increase in S. insulin 1 hour after its administration at a conventional dose (i.e. 400 mg once daily), with a downward trend in the FBS level.…”