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Serum pharmacokinetics of clindamycin hydrochloride
in normal dogs when administered at two dosage
regimens
Manolis N. Saridomichelakis*, Labrini
V. Athanasiou*†, Michel Salame*,
Manolis K. Chatzis*, Vassilis Katsoudas†
and Ioannis S. Pappas‡
*Clinic of Medicine and ‡Laboratory of Pharmacology and Toxicol-
ogy, School of Veterinary Medicine, University of Thessaly, Karditsa,
Greece
†ALAPIS S.A., Attiki, Greece
Correspondence: M. Saridomichelakis, Clinic of Medicine, School of
Veterinary Medicine, University of Thessaly, Trikalon 224, GR-43100,
Karditsa, Greece. E-mail: msarido@vet.uth.gr
This study article was published in abstract form in Veterinary Derma-
tology 2010; 21: 210.
Sources of Funding
The study was fully funded by ALAPIS S.A.
Conflict of Interest
M.N.S. has received a lecture honorarium from ALAPIS S.A. (former
VETERIN S.A.) on three occasions. L.V.A. and V.K. were employees
of ALAPIS S.A. at the time of the study.
Abstract
The aim of this cross-over study was to compare clin-
damycin pharmacokinetics in the serum of clinically
normal dogs when administered orally at two dosage
regimens (5.5 mg/kg, twice daily, and 11 mg/kg,
once daily), separated by a 1 week wash-out period.
Serum samples were obtained from six clinically
normal laboratory beagles before, 3, 6, 9 and 12 h after
the first and fifth dose of clindamycin at 5.5 mg/kg,
twice daily, and before, 3, 6, 9, 12, 18 and 24 h after
the first and third dose at 11 mg/kg, once daily.
Serum clindamycin concentrations were determined
by reverse-phase liquid chromatography coupled
with mass spectrometry. Results were analysed
using Student’s paired t-test, at a 5% level of signifi-
cance. Values of pharmacokinetic parameters that
differed significantly between the two dosage regi-
mens included the following: maximal concentration
and area under the concentration–time curve were
higher at 11 mg/kg, once daily, than at 5.5 mg/kg,
twice daily; and, more importantly, the ratio of AUC
0–24
to the minimal inhibitory concentration (MIC) value
of 0.5 lg/mL for a 24 h period (AUC
0–24
/MIC) was
higher when clindamycin was administered at 11
than at 5.5 mg/kg, at least during the first day of drug
administration. Therefore, a better pharmacokinetic
profile may be expected when clindamycin is admin-
istered at 11 mg/kg, once daily, for the treatment of
canine pyoderma caused by Staphylococcus pseudin-
termedius.
Accepted 27 January 2011
Introduction
Canine bacterial pyoderma, both superficial and deep, is
very common in everyday clinical practice. Coagulase-
positive staphylococci, especially Staphylococcus pseud-
intermedius, are the most common bacteria isolated from
the infected skin.
1–10
When skin lesions are widespread,
treatment is based on the systemic administration of anti-
microbial agents for a period that ranges from a few
weeks up to several months; topical therapy is used as an
adjunct therapy.
5,11
Clindamycin is frequently used for the treatment of
bacterial pyoderma.
5,11,12
In most studies, the in vitro
susceptibility of staphylococcal isolates from infected
canine skin to this antimicrobial agent ranges from 65 to
94%,
1,3,6,11,13–20
and the relevant figure in Greece is
80.1%.
21
Furthermore, based on four different clinical tri-
als, 71.4–100% of dogs with superficial or deep bacterial
pyoderma were cured after clindamycin administra-
tion,
2,13,14,22
and some dogs with staphylococcal isolates
showing in vitro resistance to clindamycin showed a
prompt response to the treatment.
13,14
The recommended dosage regimen of oral clindamycin
in the dog ranges from 5.5 to 11 mg/kg body weight,
given once or twice daily.
11,12
Although once-daily admin-
istration is more convenient
1,2
and seems to be effective
for the treatment of both superficial
2,13
and deep bacterial
pyoderma,
14
it is unknown whether the pharmacokinetics
of once-daily dosing are comparable to twice-daily admin-
istration.
The aim of this study was to compare the pharmacoki-
netic parameters of clindamycin when administered orally
at two dosage regimens (5.5 mg/kg body weight, twice
daily, and 11 mg/kg body weight, once daily) in clinically
normal dogs.
Materials and methods
Dogs
Six clinically normal laboratory beagles from the experimental unit
of the School of Veterinary Medicine, University of Thessaly, were
used in the study. Use of these animals was in accordance with the
ª2011 The Authors. Veterinary Dermatology
ª2011 ESVD and ACVD, Veterinary Dermatology 1
DOI: 10.1111/j.1365-3164.2011.00969.x
European Communities Council Directive 86/609/EEC and Greek
laws (1197/81 and 2015/92), the experimental protocol had been
approved by State authorities (licence no. 1381), and every effort
was made to keep their pain or discomfort to a minimum.
The six beagles included four intact males and two intact
females, with an age and body weight ranging from 11 months to
7 years (median 4 years) and from 10.1 to 20.15 kg (median
12.25 kg), respectively. Before their enrolment, all dogs were
current in their vaccinations against canine distemper, parvovirus,
viral hepatitis, leptospirosis and rabies, received regular treatment
against ecto- and endo-parasites, were fed a commercial canine
dry food at a quantity adjusted to their age and body weight, and
were housed in runs with free access outdoors. Starting 12 h
before the first dose of clindamycin and until the end of the
experimental period, the dogs were kept in clinic cages, fed twice
daily at standard times (12.00 and 24.00 h) and had ad libidum
access to water.
The inclusion criteria were as follows: (i) no history of hyper-
sensitivity to lincosamides; (ii) for female dogs, not being pregnant
or lactating; (iii) no systemic or cutaneous abnormalities detected
during physical examination; (iv) results of complete blood count
(haematocrit, haemoglobin concentration, white blood cell count,
differential cell count and platelet count), serum biochemistry
(total solids, albumin, blood urea nitrogen, creatinine, glucose, ala-
nine aminotransferase, alkaline phosphatase, calcium and phos-
phorus) and urinalysis (physical characteristics, specific gravity,
colorimetric reagent strip examination and sediment microscopy)
within reference range; (v) no administration of any kind of medi-
cation that may influence cardiovascular function, blood pressure
or cardiac output during the previous week; and (vi) no administra-
tion of systemic or topical antimicrobials during the previous
2 weeks.
Study design
The dogs were randomly divided into two treatment groups, A
(n= 3) and B (n= 3). Clindamycin hydrochloride (Clindavet
tablets,
75 and 150 mg; ALAPIS S.A., Attiki, Greece) was administered at
5.5 mg/kg orally per os (p.o.) twice daily or 11 mg/kg p.o. once daily.
Group A dogs received the 5.5 mg/kg dose twice daily for five doses
(days 1–3) and, following a 7 day washout period, then received the
11 mg/kg once daily dosing for three doses (days 11–13). Group B
dogs were treated in a similar manner except that this group received
the 11 mg/kg dose first and then the 5.5 mg/kg dose. Dogs were
fasted prior to each dosing, and medications were administered at
0.900 and 21.00 h; once daily medications were administered at
21.00 h.
Dogs were weighed 12 h before the first dose, and the number of
whole or halved tablets more closely approximating the target doses
was calculated. The dose of clindamycin base administered ranged
from 3.59 to 6.25 mg/kg (median 5.79 mg/kg) and from 10.77 to
12.5 mg/kg (median 11.58 mg/kg) for the 5.5 and the 11 mg/kg body
weight dosage, respectively. Clindavet
tablets were analysed using
reverse-phase high-performance liquid chromatography to confirm
their clindamycin base content, which was found to be in accordance
with the value given by the manufacturer (73.5 mg for the 75 mg tab-
lets and 152 mg for the 150 mg tablets).
Blood samples were obtained at 0, 3, 6, 9 and 12 h after the first
and fifth dose when dogs received the 5.5 mg/kg dose twice daily.
When dogs received the 11 mg/kg dose, blood samples were
obtained at 0, 3, 6, 9, 12 and 24 h after the first and third dose.
Blood samples were left to clot in dark for 10–20 min, and then
centrifuged at 14 187 gfor 10 min to separate serum, which was
transferred into plastic tubes and stored frozen ()20C) until analysis.
Serum clindamycin concentrations were measured in ALAPIS,
Good Laboratory Practice-accredited laboratories by reverse-phase
high-performance liquid chromatography (HPLC) coupled with mass
spectrometry. Briefly, 500 lL of water for HPLC and 80 lLof1%
H
3
PO
4
were added to 0.5 mL of serum, and the solutions were
vortexed for 3 min and centrifuged at 25 222 gfor 5 min; clinda-
mycin was then extracted using solid-phase extraction columns
(Strata-X; Phenomenex, Macclesfield, UK) and an aqueous solution
of 5% MeOH. A calibration curve was created (range 25–2500 ng/
mL); the validated limits of quantification and of detection were
50.1 and 10.5 ng/mL, respectively.
Pharmacokinetic and statistical analysis
Pharmacokinetic parameters were estimated from serum concentra-
tion–time data by noncompartmental analysis,
23,24
with the aid of
WinNonlin version 4.0.1 (Pharsight Corp., Mountain View, CA, USA).
The elimination half-life (t
½
) was determined by linear regression of
the terminal portion of the concentration–time curve, and the area
under the concentration–time curve from zero to the last measurable
concentration point (AUC
0–t
) was calculated by the linear trapezoidal
method. Then the total area under the first-moment curve (AUMC),
the mean residence time to infinity (MRT), the apparent volume of
distribution (V
d
) and the total body clearance/bioavailability (CL/F)
were calculated. The t
max
was the observed time of highest concen-
tration value and the C
max
was the observed maximal concentration;
both were taken from the data set.
The pharmacokinetic parameters calculated for each dog and
each day of drug administration included elimination rate constant
(k
el
), C
max
, dose-normalized C
max
(C
max
/dose in milligrams per
kilogram), t
max
,t
½
, AUC
0–t
, dose-normalized AUC
0–t
(AUC
0–t
/dose in
milligrams per kilogram), MRT, CL/F, time above the minimal inhibi-
tory concentration (MIC) value of 0.5 lg/mL for a 24 h period
(t> MIC) and AUC
0–24
/MIC. To exclude the possibility of a carry-
over effect from the previous administration of clindamycin at a
different dosage regimen, all pharmacokinetic parameters were
compared (Student’s unpaired t-test) between the two groups, for
the same dosage regimen and the same day of drug administration
at that regimen. The results of the two groups were combined, and
the following parameters were compared using Student’s paired
t-test: (i) k
el
,C
max
,t
max
, AUC
0–t
and CL/F between the first and third
day of drug administration at the same dosage regimen; and (ii) k
el
,
C
max
,C
max
/dose, t
max
,t> MIC, AUC
0–t
, AUC
0–t
/dose, AUC
0–24
/MIC
and CL/F between the two dosing regimens, separately for the first
and the third day of drug administration. The level of significance
was set at 0.05. All tests were performed using SPSS 13.0 (SPSS
Inc., Chicago, IL, USA).
Results
The pharmacokinetic parameters of clindamycin did not
differ between the two groups for the same dosage
regimen and the same day of drug administration,
and data were pooled. Pharmacokinetic parameters
and concentrations of clindamycin are shown in Table 1
and Figure 1, respectively.
When pharmacokinetic parameters were compared
between the first and the third day of clindamycin admin-
istration, no differences were found (Table 2).
Pharmacokinetic parameters differed significantly
between the two dosage regimens of clindamycin. More
specifically, k
el
was lower on the first day, whereas
AUC
0–t
/dose and AUC/MIC (on the first day), as well as
C
max
and AUC
0–t
(on both the first and the third day), were
higher when clindamycin was administered at the dosage
regimen of 11 mg/kg, once daily, than at 5.5 mg/kg, twice
daily (Table 2).
No adverse effects, including vomiting, occurred in any
of the dogs.
Discussion
Although food does not have a significant effect on clinda-
mycin absorption from the gastrointestinal tract,
12,25–27
ª2011 The Authors. Veterinary Dermatology
2ª2011 ESVD and ACVD, Veterinary Dermatology
Saridomichelakis et al.
dogs were fasted for 9 h prior to dosing. This was done
to minimize any possible interference by postmeal
changes in gastric motility, secretion and splachnic blood
flow.
26,28
As expected for a tablet formulation, measured
and target doses of clindamycin base were not the same;
however, we do not believe this interfered with the
results of the study because the median measured daily
dose (11.58 mg/kg body weight) was exactly the same
for both dosage regimens. For both dosage regimens,
clindamycin concentrations were measured during the
first and third day of drug administration in order to evalu-
ate trough concentrations and to examine any possible
differences over time.
A washout period of 1 week was selected based on
data that this time period should be equal to 10 elimina-
tion halflives,
28
along with data from previous publications
showing a t
½
after oral administration of clindamycin to
normal dogs usually ranging from 5 to 6 h,
25,29,30
and in
any case not exceeding 10.5 h.
31
The lack of carry-over
effect proves that the washout period was adequate for
the purposes of this study.
Most pharmacokinetic parameters found in the present
study are comparable to those previously reported
for oral administration of clindamycin at similar target
doses.
25,29–34
There are, however, two notable excep-
tions: C
max
and AUC
0–t
. Our findings are similar to those
of another study using a dose regimen of 11 mg/kg,
29
but
are substantially lower than those reported elsewhere.
During day 1 of clindamycin administration at 5.5 mg/kg,
twice daily, Weber
32
reported C
max
and AUC values of
3500 ng/mL and 25 000 h ng/mL, respectively, and dur-
ing the third day a C
max
value of 2500 ng/mL was found.
33
Moreover, C
max
and AUC values of 4300–7500 ng/mL
Table 1. Pharmacokinetic parameters for clindamycin in the serum of six clinically normal dogs, after the first (day 1) and fifth administration
(day 3) at the dosage regimen of 5.5 mg/kg, twice daily, per os (p.o.), and after the first (day 1) and third administration (day 3) at 11 mg/kg, once
daily, p.o.
Parameters
Day 1 Day 3
Median Mean SD Median Mean SD
5.5 mg/kg, twice daily, p.o.
k
el
(1/h) 0.17 0.18 0.08 0.19 0.18 0.05
C
max
(ng/mL) 1928.72 1888.28 448.59 1968.43 2007.54 803.53
C
max
/dose (10
)6
kg/mL) 350.68 343.32 81.56 357.90 365.00 146.10
t
max
(h) 3 3 — 3 3 —
t
½
(h) 4.13 4.25 1.42 3.72 4.02 1.09
t> MIC (h) 14.8 15.87 4.94 19 18 5.93
AUC
0–t
(h ng/mL) 6493.78 6703.66 1922.13 8478.00 8064.21 3627.37
AUC
0–t
/dose (10
)6
h kg/mL) 1180.69 1218.85 349.48 1541.45 1466.22 659.52
AUC
0–24
/MIC (10
)3
h) 25.98 26.81 7.69 33.91 32.26 14.51
MRT (h) 60.18 69.54 64.37 39.44 50.79 45.35
CL/F (L/h kg) 0.85 0.88 0.26 0.66 0.86 0.50
11 mg/kg, once daily, p.o.
k
el
(1/h) 0.07 0.08 0.02 0.10 0.11 0.06
C
max
(ng/mL) 3051.58 3291.67 962.86 3347.90 3491.97 920.38
C
max
/dose (10
)6
kg/mL) 277.42 299.24 87.53 304.35 317.45 83.67
t
max
(h) 3 3 — 3 3 —
t
½
(h) 9.39 9.92 2.99 7.21 7.46 2.88
t> MIC (h) 16.25 16.33 7.33 21 19.42 5.63
AUC
0–t
(h ng/mL) 18 818.90 18 352.40 5059.70 21 139.87 21 820.28 10 027.45
AUC
0–t
/dose (10
)6
h kg/mL) 1710.81 1668.40 459.97 1921.81 1983.66 911.59
AUC
0–24
/MIC (10
)3
h) 37.64 36.7 10.12 42.28 43.64 20.05
MRT (h) 39.09 96.32 123.97 12.65 40.99 53.71
CL/F (L/h kg) 0.58 0.65 0.21 0.52 0.61 0.31
Abbreviations: SD, standard deviation; k
el
, elimination rate constant; C
max
, maximal concentration; t
max
, time to maximal concentration; t
½
, elimina-
tion half-life; t> MIC, time above the minimal inhibitory concentration (MIC) value of 0.5 lg/mL for a 24 h period; AUC, area under the curve;
MRT, mean residence time; and CL/F, clearance/bioavailability.
Figure 1. Serum clindamycin concentrations for the first (upper
panel) and third day (bottom panel) at the doses of 5.5 mg/kg, twice
daily and 11 mg/kg, once daily. Data from the six dogs are pooled,
and each point represents the mean, with error bars representing the
standard deviation.
ª2011 The Authors. Veterinary Dermatology
ª2011 ESVD and ACVD, Veterinary Dermatology 3
Clindamycin pharmacokinetics in dogs
and of 36 100–52 700 h ng/mL, respectively (day 1),
32
and of 6130 ng/mL and 43 196.02 h ng/mL, respectively
(day 3),
31
after clindamycin administration at the dosage
regimen of 11 mg/kg, once or twice daily, have been pre-
viously reported. Although any direct comparison of
results from different studies is hindered by many
factors, including the small number of dogs studied, the
differences between the target and the measured doses
administered, and the timing of blood sampling, the most
plausible explanation for such constant differences may
be related to the methodology of clindamycin measure-
ment, namely microbiological, HPLC or HPLC/mass spec-
trometry. The third of these methods was used in this
study and is considered to be the most accurate,
29,35,36
and led to comparable results with a previous study using
HPLC.
29
On the contrary, all the studies showing higher
C
max
and AUC values have been based on microbiological
methods to measure clindamycin concentrations.
31–33
In
humans, clindamycin is metabolized by the cytochrome
P450 enzyme, CYP3A4, to clindamycin sulfoxide and
N-demethylclindamycin. Both metabolites have been
detected in the urine of dogs medicated with this antibac-
terial agent.
37,38
If these metabolites retain antibacterial
properties, their serum concentration will inevitably be
measured, along with that of the parent compound, when
microbiological methods are employed (i.e. in vitro inhibi-
tion of Micrococcus luteus), but not when using HPLC or
HPLC/mass spectrometry.
39
In a previous study, when clindamycin was adminis-
tered to normal dogs for 10 consecutive days at 11 mg/
kg, twice daily, the AUC was significantly lower during
the first and third day.
31
In contrast, our results show no
differences in AUC
0–t
between the first and third day of
drug administration. In accordance with our results,
increased doses of this antibacterial agent have been
reported to result in higher serum C
max
and AUC values,
32
consistent with an increase in the total amount of drug
absorbed.
Clindamycin is considered to be a bacteriostatic com-
pound, inhibiting the 50S subunit of bacterial ribosomes,
with concentration-independent and time-dependent
activity.
12,29,40
This means that serum concentrations,
which reflect interstitial fluid concentrations,
41,42
must
remain above the susceptible organism’s MIC for at least
40–67% of the dosing interval.
40,43,44
According to the
established laboratory standards, micro-organisms with
MIC <0.5 lg/mL (<500 ng/mL) are considered suscepti-
ble, those with MIC between 1 and 2 lg/mL (1000–
2000 ng/mL) are considered of intermediate susceptibility
and those with MIC >4 lg/mL (>4000 ng/mL) are consid-
ered resistant.
45,46
Although MICs of most clinical iso-
lates of S.pseudintermedius range from 0.04 to 0.4 lg/
mL (40–400 ng/mL),
30
some recent studies have shown
that, besides this being true for MIC
50
, a substantial
number of resistant isolates from dogs with bacterial pyo-
derma have resulted in MIC
90
values of >2 lg/mL
(>2000 ng/mL),
47
of >16 lg/mL (>16 000 ng/mL)
1
and
even of ‡128 lg/mL (‡128 000 ng/mL).
15
Based on
serum t> MIC, the concentrations of this antibacterial
agent are expected to be higher that the MIC breakpoint
of susceptible organisms for a substantial part (61–81%)
of the dosing interval, irrespective of the dosage regimen.
However, when considering organisms of intermediate
susceptibility, the dosage regimen of 5.5 mg/kg, twice
daily, will result in a very short period of effective con-
centrations. An additional advantage of the dosage
regimen of 11 mg/kg, once daily, may be the concentra-
tion-dependent bactericidal activity of clindamycin which,
although not widely accepted, has been found in some
studies,
12,40
coupled with its postantibiotic effect.
40,44
Finally, serum AUC
0–24
/MIC, which has been proposed as
a particularly useful parameter for clindamycin,
39
was
Table 2. Pairwise comparisons of selected pharmacokinetic param-
eters for clindamycin of six clinically normal dogs, after the first
(day 1) and/or fifth administration (day 3) at the dosage regimen of
5.5 mg/kg, twice daily, p.o., and/or after the first (day 1) and/or third
administration (day 3) at 11 mg/kg, once daily, p.o.
Parameters
Fractional
difference*† P-value 95% CI
Day 1 versus day 3 at the dosage regimen of 5.5 mg/kg, twice daily,
p.o.
k
el
1 0.994 —
C
max
0.94 0.569 —
t
max
11—
AUC
0–t
0.83 0.198 —
CL/F 1.02 0.887 —
Day 1 versus day 3 at the dosage regimen of 11 mg/kg, once daily,
p.o.
k
el
0.73 0.073 —
C
max
0.94 0.657 —
t
max
11—
AUC
0–t
0.84 0.274 —
CL/F 1.07 0.532 —
5.5 mg/kg, twice daily, p.o. versus 11 mg/kg, once daily, p.o. on
day 1
k
el
2.25 0.020 0.03–0.19
C
max
0.57 0.005 641.22–2165.55
C
max
/dose 1.15 0.164 —
t
max
11—
t> MIC 0.97 0.89 —
AUC
0–t
0.37 0.001 7305.67–15 991.82
AUC
0–t
/dose 0.73 0.029 67.43–831.68
AUC
0–24
/MIC 0.73 0.029 1.48–18.3
CL/F 1.35 0.068 —
5.5 mg/kg, twice daily, p.o. versus 11 mg/kg, once daily, p.o. on
day 3
k
el
1.64 0.051 —
C
max
0.57 0.007 615.67–2353.19
C
max
/dose 1.15 0.385 —
t
max
11—
t> MIC 0.93 0.718 —
AUC
0–t
0.37 0.014 4260.69–23 251.44
AUC
0–t
/dose 0.74 0.201 —
AUC
0–24
/MIC 0.74 0.201 —
CL/F 1.41 0.363 —
Abbreviations: 95% CI, 95% confidence interval (for simplicity values
are shown only when P< 0.05); k
el
, elimination rate constant; C
max
,
maximal concentration; t
max
, time to maximal concentration; AUC,
area under the curve; CL/F, clearance/bioavailability; t> MIC, time
above the minimal inhibitory concentration (MIC) value of 0.5 lg/mL
for a 24 h period.
*Differences are expressed as the ratio of the mean value of a given
parameter on day 1 versus day 3.
†Differences are expressed as the ratio of the mean value of a given
parameter for the dosage regimen of 5.5 mg/kg, twice daily, p.o. ver-
sus the dosage regimen of 11 mg/kg, once daily, p.o.
ª2011 The Authors. Veterinary Dermatology
4ª2011 ESVD and ACVD, Veterinary Dermatology
Saridomichelakis et al.
higher for the dosage regimen of 11 mg/kg, although sta-
tistical significance was attained only on day 1, but not on
day 3 of drug administration.
In conclusion, the results of this study show some
advantages favouring the administration of clindamycin at
the dosage regimen of 11 mg/kg, once daily, rather than
at 5.5 mg/kg, twice daily, for the treatment of canine
pyoderma caused by S.pseudintermedius. Besides the
once-daily dosing being more convenient, it will result in
an at least equipotent, or perhaps even better pharmaco-
kinetic profile.
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Re
´sume
´L’objectif de cette e
´tude croise
´ee
´tait de compare
´e la pharmacocine
´tique de la clindamycine
dans le se
´rum de chiens cliniquement sains apre
`s administration orale de deux dosages diffe
´rents
(5.5 mg/kg, deux fois par jour et 11 mg/kg, une fois par jour) se
´pare
´s d’un intervalle d’e
´limination d’une
semaine. Les e
´chantillons de se
´rum ont e
´te
´obtenus a
`partir de 6 beagles sains de laboratoire avant, 3, 6, 9
et 12 h apre
`s la premie
`re et la cinquie
`me dose de clindamycine a
`5.5 mg/kg, deux fois par jour, et avant, 3,
6, 9, 12, 18 et 24 h apre
`s la premie
`re et la troisie
`me dose a
`11 mg/kg, une fois par jour. Les concentrations
de clindamycine se
´riques ont e
´te
´de
´termine
´es par chromatographie en phase liquide inverse
´e couple
´ea
`
une spectrome
´trie de masse. Les re
´sultats ont e
´te
´analyse
´sa
`l’aide de tests t pour e
´chantillons apparie
´s,
avec un niveau de signification a
`5%. Les valeurs des parame
`tres pharmacocine
´tiques qui diffe
´raient signif-
icativement entre les deux dosages comprenaient: la concentration maximum (C
max
) et l’aire sous la
courbe de concentration en fonction du temps (AUC
0-t
)e
´tait plus e
´leve
´ea
`11mg/kg, une fois par jour qu’a
`
5.5 mg/kg, deux fois par jour. Plus important encore, le rapport entre l’ AUC
0-24
et la valeur de la concentra-
tion minimale inhibitrice (MIC) de 0.5 lg/mL pour une pe
´riode de 24 h (AUC
0-24
/MIC) e
´tait supe
´rieur quand
la clindamycine e
´tait administre
´ea
`11 mg/kg pluto
ˆt qu’a
`5.5 mg/kg, au moins au cours du premier jour
d’administration. Ainsi, un meilleur profil pharmacocine
´tique peut e
ˆtre attendu quand la clindamycine est
administre
´ea
`11 mg/kg, une fois par jour dans le traitement des pyodermites canines dues a
`Staphylo-
coccus pseudintermedius.
Resumen El propo
´sito de este estudio cruzado fue comparar la farmacocine
´tica de clindamicina en el
suero de perros clı
´nicamente normales cuando se administra por vı
´a oral en dos regı
´menes diferentes
(5,5 mg/kg dos veces al dı
´a, e 11 mg/kg una vez al dı
´a), separados por un perı
´odo de limpieza de una
semana. Se obtuvieron muestras de suero de seis perros de raza Beagle clı
´nicamente normales antes y a
las 3, 6, 9 y 12 horas tras la primera y la quinta dosis de clindamicina a la dosis de 5,5 mg/kg dos veces al
dia; y antes y a las 3, 6, 9, 12, 18 y 24 horas tras la primera y tercera dosis a la dosis de 11 mg/kg una vez la
dı
´a. Las concentraciones de clindamicina en suero fueron determinadas mediante cromatografı
´alı
´quida en
fase reversa junto a espectrofotometrı
´a de masas. Los resultados se analizaron utilizaron una prueba t-
pareada, con un 5% de nivel de significancia. Los valores de los para
´metros farmacocine
´ticos que diferı
´an
significativamente entre los dos regimenes incluyeron: concentracio
´nma
´xima (C
max
)ya
´rea de la concen-
tracio
´n bajo la curva de tiempo (AUC 0-1) que fueron mayores a la dosis de 11 mg/kg una vez al dı
´a que a la
dosis de 5,5 mg/kg dos veces al dı
´a. Au
´nma
´s importante, la relacio
´n entre AUC
0-24
con la concentracio
´n
minima inhibitoria (MIC) de 0,5 lg/ml por un periodo de 24 h (AUC
0-24
/MIC) fue mayor cuando la clindami-
cina fue administrada a 11 mg/kg que a 5,5 mg/kg, al menos durante el primer dı
´a de administracio
´n del
fa
´rmaco. Por lo tanto, se espera un mejor perfil farmacocine
´tico cuando la clindamicina se administra a
11 mg/kg para el tratamiento de la pioderma canina causada por Staphylococcus pseudintermedius.
Zusammenfassung Das Ziel dieser ‘‘Cross-over‘‘ Studie war der Vergleich der Pharmakokinetik von
Clindamycin im Serum von klinisch normalen Hunden nach oraler Verabreichung in zwei verschiedenen
Dosierungen (5,5 mg/kg, zweimal ta
¨glich, und 11 mg/kg, einmal ta
¨glich), mit einer ein-wo
¨chigen Wash-Out
Periode. Es wurden Serumproben von sechs klinisch normalen Laborbeagles genommen und zwar vor, 3,
ª2011 The Authors. Veterinary Dermatology
6ª2011 ESVD and ACVD, Veterinary Dermatology
Saridomichelakis et al.
6, 9 und 12 h nach der ersten und fu
¨nften Dosis von Clindamycin bei 5,5 mg/kg, zweimal ta
¨glich, sowie
vor, 3, 6, 9, 12, 18 und 24 h nach der ersten und dritten Dosis bei 11 mg/kg, einmal ta
¨glich. Die Serumkon-
zentrationen von Clindamycin wurden mittels Reverse-Phase Liquid Chromatographie in Kombination mit
Massenspektrometrie bestimmt. Die Ergebnisse wurden mittels gepaartem t-Test analysiert, bei einem
5% igem Signifikanzlevel. Die Werte der pharmakokinetischen Parameter, die sich bei den zwei
unterschiedlichen Dosierungen signifikant unterschieden, inkludierten: die maximale Konzentration (C
max
)
und das Gebiet unter der Konzentrationskurve (AUC
0-t
) war bei 11 mg/kg, einmal ta
¨glich, gro
¨ßer als bei
5,5 mg/kg, zweimal ta
¨glich. Noch wichtiger, das Verha
¨ltnis von AUC
0-24
zum Wert der minimalinhibitor-
ischen Konzentration (MIC) von 0,5 lg/mL fu
¨r eine 24 h Periode (AUC
0-24
/MIC) war zumindest am ersten
Tag der Medikamentenverabreichung ho
¨her, wenn Clindamycin mit einer Dosierung von 11 mg/kg statt
5,5 mg/kg verabreicht wurde. Daher ko
¨nnte ein besseres pharmakokinetisches Profil erwartet werden,
wenn Clindamycin mit 11 mg/kg einmal ta
¨glich fu
¨r die Behandlung einer durch Staphylokokkus pseudoin-
termedius verursachten caninen Pyodermie verabreicht wird.
ª2011 The Authors. Veterinary Dermatology
ª2011 ESVD and ACVD, Veterinary Dermatology 7
Clindamycin pharmacokinetics in dogs
