A Dose‐Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous Gatifloxacin in Healthy Adult Men

Gajjar, Diptee A.; LaCreta, Frank; Uderman, Howard D.; Kollia, Georgia; Duncan, Glenn F.; Birkhofer, Martin; Grasela, Dennis M.

doi:10.1592/phco.20.8.49s.35186

Cited by 59 publications

(56 citation statements)

References 19 publications

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“…8 It is recommended that the dose of gatifloxacin be reduced by 50% in patients with creatinine clearance levels of Ͻ40 or 50 mL/min. 7,8 In general, the patients in the gatifloxacin studies were significantly younger and healthier than the hospitalized patients in our cases. Because of a loss in muscle mass in elderly patients, serum creatinine levels may not be an accurate assessment of renal function.…”

Section: Discussionmentioning

confidence: 54%

“…However, no corresponding elevated insulin level was noted, and the study concluded this effect was not clinically significant. 7 Conversely, in another study, patients with type 2 diabetes who were taking glyburide were given 400 mg of gatifloxacin daily for 10 days; they showed a small increase in fasting glucose by day 4, but it was not statistically significant. 8 At doses of 200 to 800 mg, gatifloxacin's pharmacokinetics are "linear, time-independent and predictable," with the caveat "as evaluated in 40 healthy adult males."…”

Section: Discussionmentioning

confidence: 95%

“…8 At doses of 200 to 800 mg, gatifloxacin's pharmacokinetics are "linear, time-independent and predictable," with the caveat "as evaluated in 40 healthy adult males." 7 Eighty percent of the gatifloxacin is excreted in the urine unchanged, with a half-life of 7 to 14 hours. 8 It is recommended that the dose of gatifloxacin be reduced by 50% in patients with creatinine clearance levels of Ͻ40 or 50 mL/min.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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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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“…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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“…Gatifloxacin clearance in adults is 206 ml/min, with a terminal half-life of 9.4 h and a volume of distribution (Vdss) of 1.5 liter/kg, resulting in an AUC of 28.6 g ⅐ h/ml with a dose of 400 mg intravenously (11). Gatifloxacin apparent clearance in our pediatric subjects was 5.5 ml/min/kg, approximately ϳ80% higher than adults after adjustment for body weight.…”

Section: Discussionmentioning

confidence: 72%

Pharmacokinetics of Gatifloxacin in Infants and Children

Capparelli¹,

Reed

Bradley

et al. 2005

Antimicrob Agents Chemother

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Gatifloxacin is an 8-methoxy fluoroquinolone effective against a broad spectrum of pathogens common in pediatric infections. The safety and pharmacokinetics of a single dose of gatifloxacin were studied in pediatric patients from 6 months to 16 years of age. Seventy-six pediatric patients (average age, 6.7 ؎ 5.0 years) were administered a single oral dose of gatifloxacin suspension (5, 10, or 15 mg/kg of body weight; 600-mg maximum) in a dose-escalating manner. Subjects were stratified by age into 4 groups. An additional 12 children, greater than 6 years of age, received gatifloxacin as the tablet formulation at a dose of approximately 10 mg/kg. Gatifloxacin's apparent clearance and half-life were 5.5 ؎ 2.1 ml/min/kg and 5.1 ؎ 1.4 h. The maximum concentration of drug in plasma and area under the concentration-time curve (AUC) increased in a manner approximately proportional to the dose. At the 10-mg/kg dose, the bioavailability was similar between the suspension and tablet formulation. The apparent oral clearance of gatifloxacin, normalized for body weight, exhibited a small but statistically significant decrease with increasing age. In all subjects receiving gatifloxacin at 10 mg/kg, the AUC exceeded 20 g ⅐ h/ml (estimated free AUC/MIC ratio of >34 for MIC of <0.5 g/ml). These data suggest that gatifloxacin at a dose of 10 mg/kg every 24 h will achieve therapeutic concentrations in plasma in infants and children.The need for new, effective antimicrobial agents for treatment of infections caused by antibiotic-resistant bacteria has been well documented (5, 23). In infants and children, this need is exemplified by treatment failures caused by antibioticresistant strains of Streptococcus pneumoniae. This organism is the most common cause of upper and lower respiratory tract bacterial infections, bacteremia, and meningitis in the pediatric age group. Clinical isolates with documented resistance to ␤-lactams, macrolides, chloramphenicol, and sulfonamides have been noted with increasing frequency from both children and adults (12,21).Gatifloxacin is an 8-methoxy fluoroquinolone effective against a wide range of bacterial pathogens including antibiotic-resistant S. pneumoniae. This is consistent with its overall increased potency against gram-positive organisms compared to earlier fluoroquinolones, ciprofloxacin, ofloxacin, and levofloxacin. Gatifloxacin demonstrates increased activity against Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, group B streptococcus, and viridans group streptococcus (13,14,22). It also has excellent activity against a number of gram-negative enteric and respiratory pathogens including Haemophilus influenzae, Enterobacter spp., Klebsiella spp., Serratia marcescens, Legionella pneumophila, and Proteus spp. (6, 10). As a result, it is approved by the Food and Drug Administration for the treatment of community-acquired pneumonia, acute bacterial exacerbations of chronic bronchitis, sinusitis, and urinary tract infections in adults.The pharmacokinetics of gatifloxaci...

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A Dose‐Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous Gatifloxacin in Healthy Adult Men

Abstract: Gatifloxacin was safe and well tolerated at intravenous doses of up to 800 mg/day for 14 days. Gatifloxacin pharmacokinetics were linear and time independent.

Cited by 59 publications

References 19 publications

Hypoglycemia and Hyperglycemia Associated with Gatifloxacin Use in Elderly Patients

Hypoglycemia and Hyperglycemia Associated with Gatifloxacin Use in Elderly Patients

The insulinotropic effect of fluoroquinolones

Pharmacokinetics of Gatifloxacin in Infants and Children

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