Effect of Multiple‐Dose Gatifloxacin or Ciprofloxacin on Glucose Homeostasis and Insulin Production in Patients with Noninsulin‐Dependent Diabetes Mellitus Maintained with Diet and Exercise

Gajjar, Diptee A.; LaCreta, Frank; Kollia, Georgia; Stolz, Randall R.; Berger, Sheldon; Smith, William B.; Swingle, Mary; Grasela, Dennis M.

doi:10.1592/phco.20.8.76s.35182

Cited by 62 publications

(35 citation statements)

References 8 publications

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“…16,17) Gajjar et al 26) reported that, in patients with type 2 diabetes mellitus, GFLX caused an increase in serum insulin 1 h after its administration at a conventional dose, with a downward trend in the fasting glucose level. In the present study, an elevation of the serum IRI concentration was observed 1 h after the administration of GFLX at 50 or 100 mg/kg (Fig.…”

Section: Discussionmentioning

confidence: 99%

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

Ishiwata

Sanada

Yasuhara

2006

Biological & Pharmaceutical Bulletin

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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...

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Section: Discussionmentioning

confidence: 99%

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

Ishiwata

Sanada

Yasuhara

2006

Biological & Pharmaceutical Bulletin

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“…Because no patient showed any sign or symptom of hypoglycemia, the effect was determined to be not clinically significant as well. 6 A pharmacokinetic study of 40 men without diabetes monitored serum glucose and insulin levels after 200 and 400 mg of gatifloxacin was administered intravenously. After infusion, a "transient, mild to moderate decrease in fasting serum glucose" was noted for both doses.…”

Section: Discussionmentioning

confidence: 99%

Hypoglycemia and Hyperglycemia Associated with Gatifloxacin Use in Elderly Patients

Biggs¹

2003

The Journal of the American Board of Family Medicine

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Fourth-generation quinolones, such as levofloxacin (Levofloxin) and gatifloxacin (Tequin), have become widely used in outpatient and inpatient settings. These quinolones add Gram-positive bacterial coverage and maintain the Gram-negative coverage of earlier quinolones. This broad-spectrum coverage has numerous clinical applications, such as respiratory, gastrointestinal, or urinary systems infections. Because quinolones are equally bioavailable orally or intravenously, they are often used for patients at higher risk for serious infection in either outpatient or hospital settings. 1Gatifloxacin may possess some advantages over other quinolones. In vitro, gatifloxacin is 2 to 4 times more active against Streptococcus pneumoniae than levofloxacin.2 It also possesses activity against Staphylococcus aureus, some Enterococci, and atypical pathogens, such as Chlamydia pneumoniae and Mycoplasma pneumoniae.2 In our community hospital with 250 beds, it is the quinolone of choice.Within 2 months in our institution, however, 4 cases of hypoglycemia or hyperglycemia occurred in patients treated with gatifloxacin that either caused hospitalization or lengthened the patients' hospital stay. A literature search revealed no discussion about the potential severity of the hypo/ hyperglycemic side effect; thus, we briefly present these cases. Case ReportsCase 1 An 82-year-old man hospitalized for digoxin toxicity had stable serum glucoses on his glipizide (Glucotrol) 5 mg daily. In the hospital, he developed fever. The patient was allergic to penicillin and was started on gatifloxacin (Tequin) based on the empirical evidence. He received 400 mg of gatifloxacin orally and 5 mg of glipizide at 9:00 am. At noon, his capillary blood glucose was 260 mg/dL, and he received 3 units of regular insulin. By 5:00 pm, he was noted to be confused, with a serum glucose of 50 mg/dL. His hypoglycemia persisted despite intravenous glucose (100 g/L) for 12 hours. The patient was eating, and eventually his serum glucose returned to the normal range. The following morning, he again received gatifloxacin and glipizide. By 4:00 pm, he had symptomatic hypoglycemia with a serum glucose of 60 mg/dL. The gatifloxacin and glipizide were discontinued, and the patient's serum glucose increased to the 200 mg/dL level within 24 hours. The glipizide was restarted at 2.5 mg/day, and the patient's serum glucose remained stable until discharge. Case 2A 68-year-old woman with diabetes taking 1.25 mg/day of glyburide (Micronase) was hospitalized for a congestive heart failure exacerbation. Her urinalysis suggested a urinary tract infection, and the patient began receiving 200 mg/day of oral gatifloxacin. Within 24 hours, the patient developed hypoglycemia. Her capillary blood glucose was between 70 and 80 mg/dL for 2 days despite intravenous glucose and discontinuation of her glyburide. The gatifloxacin was discontinued on the fifth hospital day, and the patient's blood glucose increased to above 200 mg/dL. The glyburide was restarted and the blood glucose levels rema...

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“…We thus conclude that at 100 µM all three fluoroquinolones are in principle effective enhancers of insulin secretion, moxifloxacin being somewhat less effective than cipro-and gatifloxacin. In fact, in earlier clinical pharmacological studies on healthy and diabetic individuals, gatifloxacin was found to have the same modest effects on glucose homeostasis as ciprofloxacin and was therefore regarded as safe [23,24].…”

Section: Characteristics Of Fluoroquinolone-induced Insulin Secretionmentioning

confidence: 99%

The insulinotropic effect of fluoroquinolones

Ghaly¹,

Gunda²,

Sahin³

et al. 2009

Biochemical Pharmacology

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Effect of Multiple‐Dose Gatifloxacin or Ciprofloxacin on Glucose Homeostasis and Insulin Production in Patients with Noninsulin‐Dependent Diabetes Mellitus Maintained with Diet and Exercise

Abstract: Gatifloxacin was well tolerated in patients with NIDDM controlled by diet and exercise. It had no significant effect on glucose homeostasis, beta-cell function, or long-term fasting serum glucose levels, but it did cause a brief increase in serum insulin levels.

Cited by 62 publications

References 8 publications

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

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

Hypoglycemia and Hyperglycemia Associated with Gatifloxacin Use in Elderly Patients

The insulinotropic effect of fluoroquinolones

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