Effects of Moxifloxacin on Serum Glucose Concentrations in Rats

Acute administration of olanzapine rapidly elevates blood glucose levels. However, the mechanism underlying the rapid development of hyperglycemia with the administration of olanzapine remains unclear. The aim of the present study was to clarify the mechanism underlying olanzapine-induced acute hyperglycemia. Male Wistar rats received an intravenous infusion of saline (control) or olanzapine 2.5, 5, or 10 mg/kg. Blood samples were obtained periodically after olanzapine infusion to determine serum concentrations of glucose, olanzapine, and several endogenous substances. In a separate experiment, rats received an intravenous injection of propranolol (2 mg/kg) 30 min before infusion of olanzapine (10 mg/kg). The intravenous infusion of olanzapine induced dose-dependent increases in the serum concentrations of glucose, epinephrine, and insulin. Pretreatment with propranolol suppressed olanzapine-induced elevations in the serum concentration of glucose, but did not affect the serum concentration of olanzapine or olanzapine-induced increase in the serum concentration of epinephrine. Although the serum concentration of corticosterone increased after administration of olanzapine, no significant differences were observed among the olanzapine dose groups. Furthermore, administration of olanzapine did not affect the serum concentration of glucagon or histamine. We developed a pharmacokinetic-pharmacodynamic model assuming that the olanzapine-induced secretion of epinephrine leads to elevated serum glucose concentrations. This model appeared to satisfactorily characterize olanzapine-induced hyperglycemia. In conclusion, a single intravenous dose of olanzapine dosedependently increased the serum concentration of glucose in rats, and epinephrine plays a role in olanzapineinduced acute hyperglycemia.

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“…12,[22][23][24] On the other hand, the single intravenous injection of olanzapine did not affect the serum concentration of histamine (Fig. 4B).…”

Section: Discussionmentioning

confidence: 86%

Mechanism Underlying Induction of Hyperglycemia in Rats by Single Administration of Olanzapine

Nagata

Nakajima

Ishiwata

et al. 2016

Biological & Pharmaceutical Bulletin

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“…Our previous reports demonstrated that fluoroquinolone antimicrobial agents can induce histamine release leading to an increase in serum epinephrine concentrations and hyperglycemia. [7][8][9] In contrast, a single intravenous injection of clozapine increased the serum glucose levels without histamine release. Olanzapine also induced hyperglycemia without affecting the serum concentration of histamine.…”

Section: Discussionmentioning

confidence: 95%

“…We previously reported that novel fluoroquinolone antimicrobial agents such as gatifloxacin, levofloxacin, and moxifloxacin increased serum glucose concentrations in rats, in association with the induction of histamine release by these drugs, leading to elevations in serum adrenaline concentrations. [6][7][8][9] In contrast, a single intravenous injection of olanzapine increased the serum glucose and adrenaline levels without histamine release. 10) These results suggest that the mechanisms responsible for drug-induced elevations in serum glucose levels vary among these drugs.…”

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confidence: 94%

Clozapine-Induced Acute Hyperglycemia Is Accompanied with Elevated Serum Concentrations of Adrenaline and Glucagon in Rats

Nagata

Kimura

Ishiwata

et al. 2018

Biological & Pharmaceutical Bulletin

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Clozapine, an atypical antipsychotic agent, has been reported to cause acute hyperglycemia. However, the mechanism of clozapine-induced rapidly developing hyperglycemia is not well elucidated. To clarify the mechanism underlying clozapine-induced acute hyperglycemia, we investigated the effects of single intravenous administration of clozapine on the serum concentrations of glucose and several endogenous substances in rats. Male Wistar rats received an intravenous injection of saline (control) or clozapine 2.5, 5, 10 mg/kg. Blood samples were obtained periodically after clozapine administration to determine the serum concentrations of glucose, adrenaline, glucagon, insulin, corticosterone, and clozapine. The serum concentrations of glucose, adrenaline, and glucagon increased dose-dependently after the administration of clozapine at 2.5-10 mg/kg, and reached maxima at 5 mg/kg of clozapine. The serum concentration of corticosterone increased after the administration of clozapine, but no significant variation was observed with the dosage of clozapine. The concentration of serum insulin increased in a dose-dependent manner after clozapine administration. In conclusion, a single administration of clozapine increased the serum concentration of glucose in rats, and adrenaline and/or glucagon would be associated with clozapine-induced acute hyperglycemia.

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“…Moxifloxacin at 100 mg/kg induced histamine release, leading to increased concentrations of epinephrine and glucose in rats. 18 In contrast, a very comprehensive analysis including phase II/III clinical studies and postmarketing studies revealed that moxifloxacin did not affect glucose levels, and alterations in glucose levels were similar in patients with diabetes compared to those without diabetes mellitus. 19 In the present case, hyperglycemia might have been precipitated by 2 factors: lobar pneumonia and moxifloxacin-induced ADR.…”

Section: Discussionmentioning

confidence: 98%

Moxifloxacin-Induced Visual Hallucinations, Alterations in Mood and Behavior, and Hyperglycemia

2019

Journal of Pharmacy Practice

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Visual hallucinations are sensory perceptions that occur without external stimuli. Moxifloxacin-induced visual hallucinations are very rarely reported (<0.1%). We describe a 66-year-old woman, without any known neuropsychiatric disorder or illicit drug abuse, who experienced complex visual hallucinations, mood, and behavioral alterations secondary to peroral 1 dose of moxifloxacin treatment that persisted for approximately 36 hours. In addition, a sudden increase in her blood glucose level was noted which also improved a few days after discontinuation of moxifloxacin treatment. Although very rare, it should be kept in mind that moxifloxacin may coincidentally induce neuropsychiatric adverse effects and hyperglycemia. Clinicians should be alert to recognize such uncommon offending adverse drug reactions.

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Effects of Moxifloxacin on Serum Glucose Concentrations in Rats

Cited by 7 publications

References 26 publications

Mechanism Underlying Induction of Hyperglycemia in Rats by Single Administration of Olanzapine

Mechanism Underlying Induction of Hyperglycemia in Rats by Single Administration of Olanzapine

Clozapine-Induced Acute Hyperglycemia Is Accompanied with Elevated Serum Concentrations of Adrenaline and Glucagon in Rats

Moxifloxacin-Induced Visual Hallucinations, Alterations in Mood and Behavior, and Hyperglycemia

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