A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Cleocin Pharmacology, Pharmacokinetics, Studies, Metabolism - Clindamycin
Cleocin Pharmacology, Pharmacokinetics, Studies, Metabolism - Clindamycin
CLINICAL PHARMACOLOGY
Microbiology
Clindamycin has been shown to have in vitro activity
against isolates of the following organisms:
Aerobic gram-positive cocci,
including:
- Staphylococcus aureus,
- Staphylococcus epidermidis, (penicillinase and nonpenicillinase
producing strains). When tested by in vitro methods some
staphylococcal strains originally resistant to erythromycin
rapidly develop resistance to clindamycin,
- Streptococci (except Streptococcus
faecalis),
- Pneumococci.
Anaerobic gram-negative bacilli, including:
Bacteroides species (including Bacteroides
fragilis group and Bacteroides
melaninogenucus group), Fusobacterium species.
Anaerobic gram-positive
nonsporeforming bacilli, including:
- Propionibacterium,
- Eubacterium,
- Actinomyces species.
Anaerobic and microaerophilic
gram-positive
cocci, including:
- Peptococcus species,
- Peptostreptococcus species,
- Microaerophilic streptococci.
Clostridia: Clostridia are more resistant than most
anaerobes to clindamycin. Most Clostridium perfringens are
susceptible, but
other species, e.g.,
Clostridium sporogenes and Clostridium tertium are
frequently resistant to clindamycin. Susceptibility testing should
be done.
Cross resistance
has been demonstrated between clindamycin and lincomycin.
Antagonism has been demonstrated between clindamycin and erythromycin.
Human PHARMACOLOGY
Serum level studies with a 150 mg
oral dose
of clindamycin hydrochloride in 24 normal
adult volunteers showed
that clindamycin was rapidly absorbed after oral
administration. An average
peak serum level of 2.50
mcg/mL was reached in 45 minutes; serum
levels averaged 1.51 mcg/mL at 3 hours and 0.70 mcg/mL at 6 hours.
Absorption of an oral dose
is virtually complete (90%), and the concomitant
administration
of food does not appreciably
modify the serum concentrations;
serum levels have been
uniform and predictable
from person to person
and dose to dose. Serum
level studies following multiple doses of clindamycin hydrochloride
for up to 14 days show
no evidence
of accumulation or altered metabolism
of drug.
Serum half-life of
clindamycin is increased slightly in patients with markedly reduced
renal function. Hemodialysis
and peritoneal dialysis
are not effective in removing clindamycin from the serum.
Concentrations of clindamycin in the serum
increased linearly with increased dose. Serum levels exceed the
MIC (minimum inhibitory
concentration) for most indicated organisms for at least six hours
following administration of the usually recommended doses. Clindamycin
is widely distributed in body fluids and tissues (including bones).
The average biological
half-life is 2.4 hours. Approximately 10% of the bioactivity is
excreted in the urine and 3.6% in the feces; the remainder is excreted
as bioinactlve metabolites.
Doses of up to 2 grams of clindamycin per
day for 14 days have been well tolerated by healthy
volunteers, except that the incidence
of gastrointestinal side effects is greater with the higher doses.
No significant
levels of clindamycin are attained in the cerebro-spinal fluid,
even in the presence of inflamed meninges.
Pharmacokinetic studies in elderly volunteers (61-79 years) and younger adults
(18-39 years) indicate that age alone does not alter clindamycin pharmacokinetics
(clearance, elimination half-life, volume of distribution, and area under the serum
concentration-time curve) after IV administration of clindamycin phosphate. After
oral administration of clindamycin hydrochloride, elimination half-life is increased
to approximately 4.0 hours (range 3.4-5.1 h) in the elderly compared to 3.2 hours
(range 2.1 - 4.2 h) in younger adults. The extent of absorption, however, is not
different between age groups and no dosage alteration is necessary for the elderly
with normal hepatic function and normal (age-adjusted) renal function¹.
REFERENCES
- Smith RB, Phillips JP: Evaluation of CLEOCIN HCl and CLEOCIN Phosphate in an Aged Population. Upjohn TR 8147-82-9122-021, December 1982.
ANIMAL TOXICOLOGY
One year oral toxicity
studies in Spartan Sprague-Dawley rats and Beagle dogs at levels
up to 300 mg/kg/day (approximately 1.6 and 5.4 times the highest
recommended adult human dose based on mg/m2, respectively) have
shown clindamycin hydrochloride to be well tolerated. No
appreciable difference in pathological findings has been obtained
in groups of animals treated with clindamycin hydrochloride
from comparable control
groups. Rats receiving clindamycin hydrochloride
at 600 mg/kg/day (approximately 3.2 times the highest recommended
adult human dose based on mg/m²) for six months tolerated the drug well; however,
dogs dosed at this level (approximately 10.8 times the highest recommended
adult human dose based on mg/m²) vomited, would not eat
and lost weight.
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