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• W2023564062 abstract "Objective: Aminoglycoside antibiotics such as gentamicin have unique characteristicssuch as a strong bactericidal effect especially against gram-negative bacilli, synergisticeffects when in used combination with β-lactam antibiotics, and a postantibiotic effect (PAE). Therefore they are still widely used for the treatment of serious infection. As thetherapeutic range of gentamicin is narrow, therapeutic drug monitoring (TDM) isrecommended to avoid adverse effects such as nephrotoxicity and ototoxicity.Gentamicin is eliminated through the kidney in an unchanged form. It is reported thatcreatinine clearance depends on the time-of-day in man. Although chronopharmacokineticfindings of the drug have been reported in rodents, it is not known at presentwhether this is also the case in man or not. The purpose of this study was to clarify theeffects of the time-of-day of drug administration on the pharmacokinetics of gentamicinin man.Methods: Nine healthy male volunteers were administered gentamicin, 80 mg/body, intramuscularly at three different times of day with a washout period of more than threedays (morning ; 8: 00, evening ; 16: 00, night ; 0: 00). The subjects were randomizedusing Latin square design to receive the drug at the three different times of day.Pharmacokinetic parameters were calculated using the one compartment model withfirst order absorption.Results: Although no difference was found in Cmax and tmax of the drug among thethree dosing times, clearance of the drug at midnight was significantly lower comparedwith the other two dosing times (morning: 4.71±0.25 L/hr, evening: 4.60±0.12 L/hr, night: 4.26±0.16L/hr, mean±S. E. p <0.05). In accordance with the lower clearanceat night, the half life of the drug at night was significantly longer (morning: 1.49±0.08hr, evening: 1.52±0.11 hr, night: 1.75±0.10 hr, mean±S. E. p<0.05).Conclusions: Clearance of gentamicin depends on the time-of-day of drug administration, showing a lower clearance at night in man. This temporal variation in thepharmacokinetics of gentamicin might be clinically important in patients with someclinical situations such as renal impairment." @default.
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• W2023564062 date "1998-01-01" @default.
• W2023564062 modified "2023-10-04" @default.
• W2023564062 title "Temporal Variation in the Pharmacokinetics of Gentamicin in Man." @default.
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• W2023564062 doi "https://doi.org/10.3999/jscpt.29.855" @default.
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