Research in Veterinary Science 91 (2011) 129–131

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Research in Veterinary Science

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Pharmacokinetics and bioavailability of a long-acting formulation of cephalexin

after intramuscular administration to cats
G.A. Albarellos a,*, L. Montoya a, P.C. Quaine a, M.F. Landoni b
a
Cátedra de Farmacología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Chorroarín 280 (1427), Buenos Aires, Argentina
b
Cátedra de Farmacología, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, 60 y 118, Buenos Aires, Argentina

a r t i c l e i n f o a b s t r a c t

Article history: The pharmacokinetic profile and bioavailability of a long-acting formulation of cephalexin after intramus-
Received 1 December 2009 cular administration to cats was investigated. Single intravenous (cephalexin lysine salt) and intramuscu-
Accepted 3 August 2010 lar (20% cephalexin monohydrate suspension) were administered to five cats at a dose rate of 10 mg/kg.
Serum disposition curves were analyzed by noncompartmental approaches. After intravenous administra-
tion, volume of distribution (Vz), total body clearance (Clt), elimination constant (kz), elimination half-life
Keywords: (t½k) and mean residence time (MRT) were: 0.33 ± 0.03 L/kg; 0.14 ± 0.02 L/h kg, 0.42 ± 0.05 h1, 1.68 ±
Cephalexin
0.20 h and 2.11 ± 0.25 h, respectively. Peak serum concentration (Cmax), time to peak serum concentration
Pharmacokinetics
Cats
(Tmax) and bioavailability after intramuscular administration were 15.67 ± 1.95 lg/mL, 2.00 ± 0.61 h and
Intramuscular 83.33 ± 8.74%, respectively.
Long-acting formulation Ó 2010 Elsevier Ltd. All rights reserved.
Bioavailability

Cephalexin is a first generation cephalosporin with high activity
against Gram-positive cocci (staphylococci, streptococci) including
many beta-lactamase-producing strains, some Gram-negative
Enterobacteriaceae and anaerobes (Prescott, 2006). Cephalexin is
commonly used in the treatment of abscesses, wound and other
soft tissue infections in cats (Foster, 2004; Prescott, 2006).
Cephalexin minimum inhibitory concentrations (MIC) for sus-
ceptible bacteria ranged between 0.25–8 lg/mL (Prescott, 2006).
As for other betalactam antibiotics, cephalexin antibacterial activ-
ity is time dependent, i.e. time free drug concentration remains
above the MIC (T > MIC) being the PK/PD parameter that relates
better with clinical efficacy (Toutain et al., 2002; McKellar et al.,
2004).
Long-acting or sustained release formulations for intramuscular
administration would be a good therapeutic option when oral
administration is restricted (vomiting) or difficult (for fractious
animals) and, to facilitate owner compliance. Most oral and inject-
able formulations developed for cats are intended for b.i.d. admin-
istration (Crosse and Burt, 1984; Silley et al., 1988; Thornton and
Martin, 1997; Wackowiez et al., 1997). The purposes of this study
were to describe the pharmacokinetic profile and bioavailability of
a long-acting (once-daily) cephalexin formulation after intramus-
cular (i.m.) administration to cats.
Experimental animals were five adult mixed breed cats, weigh-
ing 4.95 ± 0.54 kg. All cats were healthy as determined by clinical
* Corresponding author. Tel.: +54 11 4524 8459; fax: +54 11 4524 8480.
E-mail address: albarell@fvet.uba.ar (G.A. Albarellos).
examination, complete blood and serum biochemical analysis
and urinalysis. Animals were housed in the UBA School of Veteri-
nary Medicine facilities. Access to high quality commercial dry
food (Fit 32Ò, Royal Canin, Argentina) and water was provided ad
libitum. All animal procedures were approved by the Institutional
Animal Care and Use Committee, School of Veterinary Science, Uni-
versity of Buenos Aires, Argentina.
An aqueous 10% (cephalexin equivalents) w/v solution of
cephalexin lysine salt (Cefalexina Richet, Richet, Buenos Aires,
Argentina) was prepared for the intravenous (i.v.) administration
(cephalic vein) and, a commercial 20% parenteral oily suspension
of cephalexin monohydrate (Cefavet, Zoovet, Buenos Aires, Argen-
tina) was used for the i.m. (dorsal lumbar muscles) administration.
Cephalexin was dosed at 10 mg/kg bodyweight according to the
manufacturer’s recommendations (10 mg/kg/24 h). A cross-over
experimental design with a two-week washout period was applied.
A jugular vein was catheterized 24 h before each study day by
using a technique previously described (Albarellos et al., 2003).
Blood samples (0.7 mL) were withdrawn at 0.083, 0.16, 0.33, 0.5,
0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 h for the i.v. route; additional sam-
ples were taken at 12, 14, 18 and 24 h after the i.m. administration.
Samples were allowed to clot at room temperature and centrifuged
at 1500g, for 15 min. The serum was frozen at 20 °C until analy-
sis. Serum samples were assayed during the week following
collection.
Cephalexin serum concentrations were determined by microbi-
ological assay (Bennet et al., 1966) using Micrococcus luteus ATCC
9341 as the test microorganism. Standard curves, in the range

0034-5288/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.rvsc.2010.08.001
130 G.A. Albarellos et al. / Research in Veterinary Science 91 (2011) 129–131

0.39 and 100 lg/mL, were prepared in normal cat serum. Each Table 1
sample was seeded in triplicate and each standard dilution in quin- Mean (±SD) pharmacokinetic parameters of cephalexin after intravenous and
intramuscular administration to cats at a dose rate of 10 mg/kg (n = 5).
tuplicate. The method was linear between 0.39 and 100 lg/mL
(r = 0.9890). Inter and intra-assay coefficients of variation were Pharmacokinetic Intravenous Intramuscular
<10%. Parameter administration administration

The limits of detection (LOD) and quantification (LOQ) of the Cmax (lg/mL) 71.31 ± 19.08 15.67 ± 1.95*
method were 0.39 lg/mL and 0.78 lg/mL, respectively. All results Tmax (h) – 2.00 ± 0.61
AUC(0–last) (lg h/mL) 71.60 ± 10.68 80.88 ± 7.69*
below the LOQ for the assay were not used in the pharmacokinetic AUC(0–1) (lg h/mL) 73.05 ± 11.23 83.42 ± 9.00*
calculations. Vz (L/kg) 0.33 ± 0.03 –
Individual cephalexin serum concentration–time curves were kz (h1) 0.42 ± 0.05 0.30 ± 0.05*
analyzed by a noncompartmental approach with a software pro- Clt (L/h kg) 0.14 ± 0.02 –
t½k (h) 1.68 ± 0.20 2.34 ± 0.38*
gram (PCNONLIN 4.0, SCI Software, Lexington, KY, USA). Major
MRT (h) 2.11 ± 0.25 4.54 ± 1.04*
pharmacokinetic parameters were calculated according to classical F (%) – 83.33 ± 8.74
equations (Gibaldi and Perrier, 1982). The observed maximum ser-
Cmax, peak serum concentration; Tmax, time to reach peak serum concentration;
um concentration (Cmax) and time of maximum serum concentra-
AUC(0–last), area under the serum concentration time curve from time zero to the last
tion (Tmax) were recorded directly from the data. The apparent measured concentration; AUC(0–1), area under the serum concentration time curve
terminal rate constant, kz, was determined by linear regression of from zero to infinity; Vz, apparent volume of distribution; kz, apparent terminal rate
the last 5–6 points on the terminal phase of the logarithmic serum constant; Clt, total body clearance; t½k, terminal half-life; MRT, mean residence
concentration vs. time curve. The bioavailability of the i.m. formu- time; F, bioavailability.
*
lation was calculated using: AUC0–1(i.m.)/AUC0–1(i.v.) *t½(i.v.)/t½(i.m.).
Significantly different (P 6 0.05).

The T > MIC was determined graphically for a MIC value of 1 lg/
mL. All values were reported as mean ± SD.
This can explain the lower bioavailability compared to intramuscu-
Statistical comparison between pharmacokinetic parameters
lar administration.
after i.v. and i.m. administration was performed using a paired t
For betalactams, it has been reported that the PK/PD breakpoint
test (Wilcoxon) and the significance level was P 6 0.05.
recommended for efficacy (T > MIC) should be 50–80% of the
The mean serum concentration–time curves following the i.v.
dosing interval (McKellar et al., 2004; Toutain et al., 2002). In
and i.m. cephalexin are shown in Fig. 1. Estimated pharmacokinetic
the present study this goal has been achieved for the i.m. adminis-
parameters for both routes are summarized in Table 1. All PK
tration, since serum cephalexin concentrations remain above a
parameters estimated after i.m. administration were statistically
MIC of 1 lg/mL for at least 12 h. However, doses reported here
different from those estimated after i.v. administration (P 6 0.05).
for this long-acting – once-daily – formulation of cephalexin
Adverse effects were not observed during or following cepha-
should be tested in clinical trials to properly establish its clinical
lexin i.v. or i.m. administration in any of the cats.
efficacy.
Cephalexin pharmacokinetic parameters obtained in this study
were similar to those reported by other authors (Crosse and Burt,
Acknowledgments
1984; Silley et al., 1988; Thornton and Martin, 1997; Wackowiez
et al., 1997).
We are grateful to Royal Canin, Argentina, for the kind provision
After i.m. administration, the high bioavailability (F: 83.33 ±
of the animal food. This work was supported by a grant of UBACyT,
8.74%) reflects a good absorption. This value is significantly higher
Project V002 2008–2010.
than that reported for cats after oral administration (F: 56%)
(Wackowiez et al., 1997) as well as, for dogs after oral and paren-
teral administration (60%) (Carli et al., 1999; Chicoine et al., References
2009). It is important to highlight that after oral administration Albarellos, G.A., Bonafine, R.R., Kreil, V.E., Ambros, L.A., Montoya, L., Hallu, R.E., 2003.
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