Absorption kinetics and bioavailability of cephalexin in the dog after oral and intramuscular administration

Carli, S.; Anfossi, P.; Villa, Roberto Edoardo; Castellani, G; Mengozzi, G; Montesissa, Clara

doi:10.1046/j.1365-2885.1999.00208.x

Cited by 25 publications

(30 citation statements)

References 24 publications

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“…The pharmacokinetic parameters calculated in this study after the 10 : 00 h administration are similar to those previously reported by other authors after the oral administration of cephalexin to dogs (Campbell & Rosin, 1998;Carli et al, 1999;Crosse & Burt, 1984;Silley et al, 1988). A. P. Prados et al 166 This study further compared these pharmacokinetic parameters to those calculated after the 22 : 00 h administration in order to explore the hypothesis that absorption would be less and elimination slower when cephalexin was orally administered to dogs during the rest phase.…”

Section: Discussionsupporting

confidence: 83%

“…In the present study, C max was decreased significantly to almost 77% of its value after cephalexin was administered at nighttime, without varying the time during the 12 h dosing interval when peak concentration was obtained. PEPT1 mediates the intestinal absorption of cephalexin in rats, humans (Berlioz et al, 1999;Buyse et al, 2001;Ganapathy et al, 1995), and most probably dogs (Carli et al, 1999); additional mechanisms, such as passive diffusion, are of minor importance due to the low lipophilicity of the medication (Berlioz et al, 1999). Previous studies have demonstrated that the intestinal permeability of cephalexin is directly proportional to PEPT1 expression in Caco-2/hPEPT1 cells and in rat intestinal mucosa (Chu et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Chronopharmacological Study of Cephalexin in Dogs

Prados

Ambros

Montoya

et al. 2007

Chronobiology International

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“…This values is similar to that reported for dogs (60%) (Carli et al, 1999;Chicoine et al, After multiple administration bioavailability was higher (p<0.05), this difference could be reflecting the improvement of absorption when small volumes are injected (Zuidema et al, 1994).…”

Section: Resultssupporting

confidence: 89%

“…This is consequence of the high inter-animal variation observed, especially, after IV and single IM administration. The estimated valueswere similar to that in other species such as, rat (Tsai et al, 2000) dog (Carli et al, 1999) and cat (Albarellos et al, 2011). Accumulation index after multiple administrationswas closed to 1, reflecting cephalexin low accumulation capacity.Similar values are reported for humans after repeated oral administration (Pfeffer et al, 1977).…”

Section: Resultssupporting

confidence: 84%

Pharmacokinetics of Cephalexin after Intravenous and Single and Multiple Intramuscular Administration to Rabbit

Meneses¹,

Albarellos²,

Landoni³

2014

IJVMR

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Cephalexin is a first generation cephalosporin widely used in rabbits. Its spectrum includes Pasteurella multocida and Staphylococcus aureus. These bacteria, together with Bordetella bronchiseptica, are the main cause of respiratory infections. Although many textbooks on rabbit therapeutics report the use of cephalexin, including administration schedules, there are not published papers on the pharmacokinetics of cephalexin after IV and IM administration to rabbit. Therefore, the objective of the present study was to describe cephalexin disposition in rabbits after intravenous and single and multiple intramuscular administrations. Three administration schedules were studied: single IV administration (10 mg/kg), single IM administration (10 mg/kg) and multiple IM administration (2.5 mg/kg/6). Serial blood samples were collected over a 24 h period. Cephalexin plasma concentrations were determined by microbiological method using Kocuria rhizophila ATCC 9341 as microorganism test. No statistical differences were observed between routes of administration for any of the estimated PK parameters. The unique difference was observed on bioavailability between intramuscular administration schedules. Elimination half-life was 1.45, 1.09 and 1.91 h for the single IV, single IM and multiple IM administration, respectively. Bioavailability after single and multiple IM administration was 47 and 97.5%, respectively. After multiple IM administration maximum and minimum plasma concentration at steady state were 2.77 and 0.34 µg/ml, while Cmax after single IM administration was 9. 22 µg/ml.Considering that for betalactams the PK/PD breakpoint recommended for efficacy (T > MIC) should be 50-80% and that the reported MIC for most gram-positive organisms and Pasteurella multocida is ≤1.0 μg/ml, the present study demonstrates that a single IM dose of 10 mg/kg/24 h is enough to maintain therapeutic concentrations for a 24 hours period. When a 2.5mg/kg dose is used administration every 6 hours is recommended.

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“…As in this study for cefotaxime, cephalosporins seem to be rapidly cleared in dogs. Carli et al (1999) suggested a dose interval of 6 to 8 h for cephalexin after i.m. administration, but much faster elimination rates have been found (Schermerhorn et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and clinical efficacy of cefotaxime for the treatment of septicaemia in dogs

López

Gutiérrez

Ocampo

2004

Acta Veterinaria Hungarica

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Considering the already known pharmacological features of cefotaxime, a study with two approaches of pharmacokinetics and clinical efficacy in septicaemic dogs was carried out. Pharmacokinetic variables were defined for doses of 10 mg/kg, and 20 mg/kg, utilising a quantitative bacteriological analysis. Values for half-life (T½ß) at 10 mg/kg were 0.8, 1.48 and 1.52 h for the i.v., s.c. and i.m. routes, respectively. Corresponding values for the 20 mg/kg dose for the same routes were 0.8, 1.49 and 1.53 h, respectively. Relatively fast clearance (ranging from 0.58 to 0.64 L/kg/h) allowed a maximum dose interval of 12 h. The above-stated doses of cefotaxime were administered i.v. to 40 cases of septicaemia, clinically divided into 20 moderately severe cases treated with 10 mg/kg i.v., of cefotaxime bid, and 20 severe ones, treated with 20 mg/kgi.v. of cefotaxime bid. Injections continued until a previously defined criterion of 'clinically recovered' was obtained. Thereafter, a follow-up treatment was established using the same dose and dose-interval but through the s.c. route. Due to the apparent volumes of distribution obtained (ranging from 0.48 to 0.51 L/kg), considering the overall clinical efficacy obtained (90% for the 10 mg/kg dose and 75% for the 20 mg/kg dose), and due to the rapid improvement observed after a few doses of the drug (1.8 to 2.5 doses to 'clinical improvement'), it is safe to postulate such doses of cefotaxime as excellent choices for the treatment of septicaemia in dogs.

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Absorption kinetics and bioavailability of cephalexin in the dog after oral and intramuscular administration

Cited by 25 publications

References 24 publications

Chronopharmacological Study of Cephalexin in Dogs

Chronopharmacological Study of Cephalexin in Dogs

Pharmacokinetics of Cephalexin after Intravenous and Single and Multiple Intramuscular Administration to Rabbit

Pharmacokinetics and clinical efficacy of cefotaxime for the treatment of septicaemia in dogs

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