Daily Variations in Ceftriaxone Pharmacokinetics in Rats

Rebuelto, M.; Ambros, L.; Rubio, María Dolores Mesa

doi:10.1128/aac.47.2.809-812.2003

Cited by 14 publications

(22 citation statements)

References 29 publications

(19 reference statements)

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“…The biliary and renal clearances of ampicillin were significantly higher during the active compared with sleep cycle of rats (White et al, 1995;Mesnard-Ricci and White, 1998). The disposition of ceftriaxone in the rat exhibited significant daily changes attributed mainly to an enhanced excretion during the active period (Rebuelto et al, 2003b). Thus, the finding of a higher clearance of gentamicin during the daytime (08:00 h) in day-active dogs observed in our study is consistent with the greater elimination of other hydrophilic drugs in the active phase of various other species.…”

Section: Discussionmentioning

confidence: 95%

“…Chronokinetics is the study of biological rhythmdependent differences in drug absorption and disposition according to the time of day when medications are administered. Several authors have reported temporal variations in the pharmacokinetics of antimicrobial drugs, such as aminoglycosides (Lin et al, 1994;Bleyzac et al, 2000), betalactams (White et al, 1995;Mesnard-Ricci and White, 1998;Rebuelto et al, 2003a), and fluoroquinolones (Sarveshwer Rao et al, 1997;Rebuelto et al, 2003b). Moreover, previous studies on laboratory animals have shown temporal variations in the renal toxicity induced by tobramycin (Lin et al, 1994), isepamicin (Yoshiyama et al, 1993), and gentamicin (Beauchamp et al, 1997) with a peak observed when treatment is administered during the resting period, and a trough when given during the activity period.…”

Section: Introductionmentioning

confidence: 92%

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Chronopharmacokinetic Study of Gentamicin in Dogs

Widerhon

Díaz

Picco

et al. 2005

Chronobiology International

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The purpose of this experiment was to determine whether the time of day of single intravenous doses of gentamicin affects the drug's pharmacokinetics in dogs maintained under a 12 h light (08:00 to 20:00 h), 12 h dark (20:00 to 08:00 h) cycle. Using a crossover design, 6 mixed-breed male dogs received a single dose of 2 mg/kg of gentamicin at 8:00 or 20:00 h. Serial blood samples were collected and pharmacokinetic parameters were calculated following each timed dose. The concentration of the antibiotic was lower following the 08:00 h compared to the 20:00 h administration. When gentamicin was administered at 20:00 h, the initial concentration, mean residence time, and area under the disposition curve were significantly higher (p < 0.05) and the apparent volume of distribution of the central compartment, apparent volume of distribution, apparent volume of distribution at steady-state, and total body clearance (1.73+/-0.55 at 20:00 h versus 3.31+/-0.67 L/min/kg at 08:00 h) were significantly lower than for the 08:00 h administration (p < 0.05). Our results show that the pharmacokinetics of gentamicin exhibits significant temporal variation when administered to dogs at different times of day.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 92%

Chronopharmacokinetic Study of Gentamicin in Dogs

Widerhon

Díaz

Picco

et al. 2005

Chronobiology International

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“…In human beings, ciprofloxacin (Sarveshwer Rao et al, 1997) and amikacin (Bleyzac et al, 2000) urinary elimination was greater in the morning than evening. The renal excretion of ampicillin (White et al, 1995), norfloxacin (Rebuelto et al, 2003a), and ceftriaxone (Rebuelto et al, 2003b) was significantly higher during the active compared with the sleep cycle of rats. In dogs administered gentamicin at different times of day, total drug clearance exhibited its minimum during the nighttime (Widerhon et al, 2005).…”

Section: Discussionmentioning

confidence: 98%

Chronopharmacological Study of Cephalexin in Dogs

Prados

Ambros

Montoya

et al. 2007

Chronobiology International

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Recent studies have identified a 24 h rhythm in the expression and function of PEPT1 in rats, with significantly higher levels during the nighttime than daytime. Similarly, temporal variations have been described in glomerular filtration rate and renal blood flow, both being maximal during the activity phase and minimal during the rest phase in laboratory rodents. The aim of this study was to assess the hypothesis that the absorption of the first-generation cephalosporin antibiotic cephalexin by dogs would be less and the elimination would be slower after evening (rest span) compared to morning (activity span) administration, and whether such administration-time changes could impair the medication's predicted clinical efficacy. Six (3 male, 3 female; age 4.83+/-3.12 years) healthy beagle dogs were studied. Each dog received a single dose of 25 mg/kg of cephalexin monohydrate per os at 10:00 and 22:00 h, with a two-week interval of time between the two clock-time experiments. Plasma cephalexin concentrations were determined by microbiological assay. Cephalexin peak plasma concentration was significantly reduced to almost 77% of its value after the evening compared to morning (14.52+/-2.7 vs. 18.77+/-2.8 microg/mL) administration. The elimination half-life was prolonged 1.5-fold after the 22:00 h compared to the 10:00 h administration (2.69+/-0.9 vs. 1.79+/-0.2 h). The area under the curve and time to reach peak plasma concentration did not show significant administration-time differences. The duration of time that cephalexin concentrations remained above the minimal inhibitory concentrations (MIC) for staphylococci susceptiblity (MIC=0.5 microg/mL) was>70% of each of the 12 h dosing intervals (i.e., 10:00 and 22:00 h). It can be concluded that cephalexin pharmacokinetics vary with time of day administration. The findings of this acute single-dose study require confirmation by future steady-state, multiple-dose studies. If such studies are confirmatory, no administration-time dose adjustment is required to ensure drug efficacy in dogs receiving an oral suspension of cephalexin in a dosage of 25 mg/kg at 12 h intervals.

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“…Two days before treatment inception, a brief startle session was performed to obtain experimental and control groups matched for startle reactivity (matching session; Geyer and Swerdlow, 1998;Martinez et al, 1999). In all experimental groups, PPI test was conducted at day 10 (2 days after CEF withdrawal) to allow complete clearance of the antibiotic (Rebuelto et al, 2003), 30 min after the injection of saline or LY379268.…”

Section: Ppi Of the Startle Reflexmentioning

confidence: 99%

The mGluR2/3 Agonist LY379268 Blocks the Effects of GLT-1 Upregulation on Prepulse Inhibition of the Startle Reflex in Adult Rats

Bellesi

Conti

2010

Neuropsychopharmacol

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The main glutamate transporter GLT-1 is responsible for clearing synaptically released glutamate from the extracellular space and contributes to the shaping of glutamatergic transmission. Recently, it has been shown that ceftriaxone (CEF)-induced GLT-1 upregulation is associated with an impairment of the prepulse inhibition (PPI) of the startle reflex, a simple form of information processing that is reduced in schizophrenia, and determines a strong reduction in hippocampal metabotropic glutamate receptor (mGluR)2/3-dependent long-term depression. In this study, we tested the hypothesis that administration of the mGluR2/3 agonist LY379268 blocks the effect of GLT-1 upregulation on PPI of the startle. We showed that administration of LY379268 (1 mg/kg) prevented PPI alterations associated with GLT-1 upregulation, suggesting that CEF-induced PPI impairment was mGluR2/3 dependent. In addition, we showed that CEF-induced GLT-1 upregulaton did not alter the expression of mGluR2/3, and also that it occurred at sites of mGluR2/3 expression. These results indicate a novel mechanism by which GLT-1 upregulation modulates PPI of the startle.

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Daily Variations in Ceftriaxone Pharmacokinetics in Rats

Cited by 14 publications

References 29 publications

Chronopharmacokinetic Study of Gentamicin in Dogs

Chronopharmacokinetic Study of Gentamicin in Dogs

Chronopharmacological Study of Cephalexin in Dogs

The mGluR2/3 Agonist LY379268 Blocks the Effects of GLT-1 Upregulation on Prepulse Inhibition of the Startle Reflex in Adult Rats

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