Clindamycin Injection - Pharmaceutical Information, Clinical Trials, Detailed Pharmacology, Toxicology
Россия
  • Россия
  • Украина

Clindamycin Injection - Scientific Information

Manufacture: Fresenius Kabi USA, LLC
Country: Canada
Condition: Bacteremia, Bacterial Infection, Bacterial Vaginitis, Pneumonia, Sinusitis, Skin or Soft Tissue Infection, Toxoplasmosis, Prophylaxis, Toxoplasmosis
Class: Antibiotics/antineoplastics, Lincomycin derivatives
Form: Liquid solution, Intravenous (IV)
Ingredients: Clindamycin phosphate, edetate disodium, benzyl alcohol, sodium hydroxide, hydrochloric acid.

Pharmaceutical Information

Drug Substance

Proper Name: clindamycin phosphate
Chemical Name:
  1. L-threo-α-D-galacto-Octopyranoside, methyl 7-chloro-6,7,8-trideoxy-6-[[(1-methyl-4-propyl-2-pyrrolidinyl)carbonyl]amino]-1-thio-,2-(dihydrogen phosphate), (2S-trans)-
  2. Methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pryrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside 2-(dihydrogen phosphate)
  3. 7(S)-Chloro-7-deoxylincomycin 2-phosphate
Structural Formula:

Molecular Formula: C18H34C1N2O8PS
Molecular Weight: 504.96 g/mol
Description: Clindamycin phosphate is a water soluble ester of clindamycin and phosphoric acid. It is a white to off-white crystalline hygroscopic powder that is odourless or nearly odourless. It has a pH of 3.5 to 4.5 and melts with decomposition at about 175°C. The partition coefficient is 0.03.

Composition

Each mL of Clindamycin Injection contains clindamycin phosphate equivalent to 150 mg clindamycin base, benzyl alcohol 9.45 mg, edetate disodium 0.5 mg, and Water for Injection q.s.

When necessary, the pH is adjusted with sodium hydroxide and/or hydrochloric acid to maintain a pH range of 5.5 to 7.0.

Stability and Storage Recommendations

Store Clindamycin Injection at room temperature between 15 °C and 30 °C.

Parenteral Products

All parenteral products should be visually inspected for haziness, particulate matter, discolouration and leakage prior to administration.

Preparation for Intravenous Use

Clindamycin Injection was found to be physically compatible and demonstrated no significant change in pH or antimicrobial potency over a period of 24 hours when 4 mL (600 mg) was diluted with 1000 mL of the following commonly used infusion solutions:

  • Sodium Chloride Injection
  • 5% Dextrose Injection
  • Lactated Ringer's Injection

It is recommended that intravenous admixtures be stored no longer than 24 hours at room temperature or 72 hours when refrigerated (2 °C – 8 °C).

As with all parenteral products, intravenous admixtures should be inspected for clarity of solutions, particulate matter, precipitate, discolouration, and leakage prior to administration whenever solution and container permit. Solutions showing haziness, particulate matter, precipitate, discolouration or leakage should not be used.

Compatibility With Other Products

Clindamycin phosphate was not stable when added to Dextrose 5% in water plus vitamins. Although Clindamycin Injection is compatible with Dextrose 5% in water, it is not recommended that Clindamycin Injection be mixed with any infusion solutions containing B vitamins.

Clindamycin phosphate has been shown to be compatible with gentamicin sulfate, tobramycin sulfate and amikacin sulfate. However, a precipitate has been observed when clindamycin phosphate and gentamicin are drawn undiluted into the same syringe before subsequent dilution. This precipitate appears to be a zinc-clindamycin complex which results from the zinc content of some gentamicin products. The particle size of the insoluble material is very small and disappears when the admixture is shaken. To avoid this problem, do not mix Clindamycin Injection and gentamicin sulfate prior to dilution. Rather, dilute one drug or the other, agitate the solution and then add the second antibiotic.

Incompatibility With Other Products

When combined with Clindamycin Injection in an infusion solution, ampicillin, phenytoin sodium, barbiturates, aminophyllin, calcium gluconate, magnesium sulfate, ceftriaxone sodium, and ciprofloxacin are each physically incompatible with clindamycin phosphate.

Availability of Dosage Form

Clindamycin Injection is available as follows:

  • 300 mg/vial, 2 mL fill in 2 mL, Multiple-dose, flip-top vials in packages of 25.
  • 600 mg/vial, 4 mL fill in 6 mL, Multiple-dose, flip-top vials in packages of 25.
  • 900 mg/vial, 6 mL fill in 6 mL, Multiple-dose, flip-top vials in packages of 25.

Discard within 28 days after the initial puncture.

Clindamycin Injection is also available in a 60 mL (150 mg/mL) fill in 60 mL Single Use Pharmacy Bulk Vial.

The availability of the Pharmacy Bulk Vial is limited to hospitals with a pharmacy based IV admixture program. The Pharmacy Bulk Vial is intended for single puncture, multiple dispensing for intravenous use only.

Must be diluted before use; contents of the vial must be dispensed within 24 hours of initial entry.

Microbiology

Clindamycin phosphate is inactive in vitro, but is rapidly converted in vivo to the antibacteriallyactive clindamycin.

In order to assess the significance of in vitro antibiotic activity against bacterial species, it is necessary to compare the organism's minimum inhibitory concentration (MIC) to the defined susceptibility interpretive breakpoints for the antibiotic. Table 1 identifies the currently-accepted NCCLS (1990) MIC interpretative breakpoints for clindamycin.

Table 1: MIC Breakpoints for Clindamycin (μg/mL)
Suspectible Intermediate Resistant
Aerobic bacteria ≤ 0.50 1 – 2 ≥ 4
Anaerobic bacteria ≤ 4.0 - ≥ 8

The reported clindamycin MIC90 value (i.e., the concentration of clindamycin that inhibits 90% of test isolates) was utilized as the most descriptive measure of clindamycin activity. Where the data from more than one study are summarized, the weighted average MIC90 value was calculated to account for differences in the number of strains in each study.

The in vitro susceptibility of clinical isolates to clindamycin is presented in Table 2 (gram-positive aerobic bacteria), Table 3 (gram-negative aerobic bacteria), Table 4 (gram-positive anaerobic bacteria), Table 5 (gram-negative anaerobic bacteria) and Table 6 (Chlamydia spp and Mycoplasma spp).

Table 2: In vitro Activity of Clindamycin Against Gram-Positive Aerobic Bacteriaa
Organism Nb MIC90 Rangec MIC90d
Bacillus cereus 46 1 1
Corynebacterium diphtheriae 192 0.1 0.1
Listeria monocytogenes 218 1 – 8 2.22
Staphylococcus aureus
(methicillin-susceptible)
286 0.12 – 2 0.50
Staphylococcus saprophyticus 57 0.12 – 0.25 0.16
Streptococcus agalactia 59 ≤ 0.06 – 0.50 0.15
Streptococcus bovis 22 0.04 0.04
Streptococcus pneumoniae
(penicillin-susceptible)
660 0.03 – 0.25 0.23
Streptococcus pyogenes 141 0.13 – 0.25 0.08
Streptococcus spp, Group B 38 ≤ 0.12 – 0.25 0.15
Streptococcus spp, Group C 30 ≤ 0.12 – 0.50 0.22
Streptococcus spp, Group G 34 0.06 – 0.50 0.31
Streptococcus spp, viridans Group
(penicillin-susceptible)
67 ≤ 0.06 – 1.6 0.53

aClinical efficacy has not been established for some of these species

bN, total number of isolates

cRange of reported MIC90 values

dMIC90 for single study or weighted average MIC90 for two or more studies

Table 3: In vitro Activity of Clindamycin Against Gram-Negative Aerobic Bacteriaa
Organism Nb MIC90 Rangec MIC90d
Campylobacter jejuni 449 0.39 - 8 1.7
Campylobacter fetus 41 1 - 1.6 1.2
Campylobacter coli 31 0.50 0.50
Gardnerella vaginalis 156 ≤ 0.06 – 0.39 0.3
Helicobacter pylori 47 2 - 3.1 2.6
Neisseria gonorrhoeae
(β-lactamase-negative)
77 4 4
Neisseria gonorrhoeae
(β-lactamase-positive)
54 2 2

aClinical efficacy has not been established for some of these species

bN, total number of isolates

cRange of reported MIC90 values

dMIC90 for single study or weighted average MIC90 for two or more studies

Table 4: In vitro Activity of Clindamycin Against Gram-Positive Anaerobic Bacteriaa
Organism Nb MIC90 Rangec MIC90d
Actinomyces israelii 46 0.12 0.12
Actinomyces spp 38 0.50 - 1 0.8
Clostridium botulinum 224 4 4
Clostridium difficile 191 4 - > 256 57.7
Clostridium novyi 18 2 2
Clostridium perfringens 386 0.25 - 8 3.4
Clostridium ramosum 98 4 - 12.5 8.3
Eubacterium spp 45 0.4 - 2 1.1
Lactobacillus spp 88 0.50 - 1 0.8
Peptostreptococcus anaerobes 283 0.25 - 0.50 0.4
Peptostreptococcus asaccharolyticus 268 0.25 - 2 1.5
Peptostreptococcus magnus 90 2 2
Peptostreptococcus prevotii 87 0.12 - 4 2.9
Peptostreptococcus tetradius 28 0.5 0.5
Anaerobic gram-positive cocci 247 0.5 - 1 0.9
Propionibacterium acnes 267 0.10 - 0.25 0.2
Propionibacterium spp 71 0.12 - 0.20 0.16

aClinical efficacy has not been established for some of these species

bN, total number of isolates

cRange of reported MIC90 values

dMIC90 for single study or weighted average MIC90 for two or more studies

Table 5: In vitro Activity of Clindamycin Against Gram-Negative Anaerobic Bacteriaa
Organism Nb MIC90 Rangec MIC90d
Bacteroides fragilis group 4284 0.5 - 8 2.45
Bacteroides fragilis 2002 ≤ 0.20 – 4 2.22
Bacteroides melaninogenicus 224 ≤ 0.03 – 0.50 0.07
Bacteroides spp 141 ≤ 0.06 – 0.50 0.31
Bacteroides bivius 155 ≤ 0.03 - ≤ 0.05 ≤ 0.11
Bacteroides disiens 33 ≤ 0.03 - ≤ 0.06 ≤ 0.05
Fusobacterium spp 330 ≤ 0.10 – 2 0.85
Mobiluncus mulieris 10 0.06 0.06
Mobiluncus curtisii 12 0.12 0.12
Veillonella spp 38 0.06 - 0.25 0.20

aClinical efficacy has not been established for some of these species

bN, total number of isolates

cRange of reported MIC90 values

dMIC90 for single study or weighted average MIC90 for two or more studies

Clindamycin has demonstrated in vitro activity against Chlamydia trachomatis and Mycoplasma spp (see Table 6). For Chlamydia trachomatis, the MIC90 for clindamycin is reached at 2.3 μg/mL; in vitro synergism with gentamicin has also been demonstrated.

Table 6: In vitro Activity of Clindamycin Against Chlamydia spp and Mycoplasma sppa
Organism Nb MIC90 Rangec MIC90d
Chlamydia trachomatis 84 0.5 – 5.9 2.3
Mycoplasma hominis 106 0.25 – 0.8 0.58
Mycoplasma pneumoniae 9 4 4

aClinical efficacy has not been established for some of these species

bN, total number of isolates

cRange of reported MIC90 values

dMIC90 for single study or weighted average MIC90 for two or more studies

The in vitro activity of clindamycin in combination with primaquine has not been determined.

Development of resistance to clindamycin by staphylococci is slow and stepwise rather than rapid and streptomycin-like. Clindamycin, like lincomycin, participates in the dissociated crossresistance phenomenon with erythromycin. Clindamycin is not cross-resistant with penicillin, ampicillin, tetracycline or streptomycin. It is, however, cross-resistant with lincomycin.

Resistance to clindamycin may occur by one of several mechanisms. Resistance does not appear to be caused by reduced drug uptake but rather is generally due to alterations in the bacterial target site (50S ribosomal subunit). Resistance can result from either changes in a ribosomal protein at the receptor site or a change in the 23S ribosomal RNA by methylation of adenine. Rare isolates of staphylococci and some veterinary isolates of streptococci may enzymatically inactivate clindamycin by adenylation. Plasmid-mediated transferable resistance to clindamycin (and erythromycin) in B.fragilis was reported in 1979. Despite the existence of multiple resistance mechanisms, the reported incidence of clindamycin resistance in the B.fragilis group has remained relatively low (averaging 5.3% from 1970 - 1987 in over 7,600 isolates). Susceptibility of isolates to clindamycin should be assessed by individual MIC determinations.

Pharmacology

Absorption and Excretion in Normal Human Volunteers

Clindamycin phosphate is essentially inactive as the phosphate ester. Chemical or enzymatic hydrolysis of clindamycin phosphate is necessary to obtain the antibiotic activity of the clindamycin base. When tested with commercial human serum, clindamycin at a concentration of 1 mcg/mL of clindamycin free base is 92.8% protein bound.

Intramuscular

Serum levels and urinary excretion of clindamycin and clindamycin phosphate were measured after the single administration of 300 mg (2 mL) base equivalent of clindamycin phosphate and multiple dose administration (300 mg every 8 hours for 14 days). The results are shown in Table 7.

Table 7: Mean Serum Levels in mcg/mL of Free Clindamycin and Clindamycin Phosphate After 1st and 43rd IM Dose of 300 mg (2 mL) of Clindamycin Phosphate
Hours After Injection
1st Injection 43rd Injection
0.5 1 1.5 2 3 4 7.5 0 7.5
Free clindamycin 2.05 3.16 3.66 3.88 3.89 3.56 1.94 2.85 2.67
Clindamycin
phosphate
2.40 1.99 1.75 1.33 0.86 0.59 0.03 0.04 0.06

The apparent half-life of clindamycin phosphate is 3.5 to 4.5 hours. Bioavailability of clindamycin from its phosphate was estimated to be greater than 75%, based on urinary excretion of free clindamycin bioactivity (0 to 12 hours). During the multiple dose studies (300 mg every 8 hours for 14 days), there was no evidence of drug accumulation or enzyme induction.

Intravenous

Determination of serum levels of clindamycin and clindamycin phosphate after intravenous infusion of 300 to 1200 mg free base equivalents of clindamycin phosphate indicated that the concentrations of free clindamycin and intact phosphate were approximately equivalent during rapid infusion (see Table 8). The mean half-life of free clindamycin given by intravenous infusion is 2.28 hours for a 300 mg dose, 2.94 hours for a 600 mg dose, 3.27 hours for a 900 mg dose and 3.07 hours for a 1200 mg dose.

During maintenance infusion, free clindamycin (3.6 to 6.9 mcg/mL) was the predominant species in circulation. Over the total infusion period (0 to 8 hours) clindamycin and clindamycin phosphate were excreted in the urine in amounts up to 12.3% and 5.1% respectively of the administered clindamycin phosphate dose. There was no indication that the capacity to excrete clindamycin in the urine had been taxed by these dosages.

Table 8: Mean Serum Levels in mcg/mL of Free Clindamycin and Clindamycin Phosphate After Intravenous Infusion of 300, 600, 900 and 1200 mg of Clindamycin Phosphate
Dosage and Rate of Infusion Time After Infusion Began (in hours)
A* B* 1.5 4 12
300 mg in
10 minutes
Free
clindamycin
5.40 4.36 3.49 1.66 0
Clindamycin
phosphate
14.66 2.35 0.43 0.13 -
600 mg in
20 minutes
Free
clindamycin
8.42 6.70 5.88 3,.04 0.62
Clindamycin
phosphate
26.98 2.24 0.58 0.28 0.02
900 mg in
30 minutes
Free
clindamycin
10.37 8.02 7.10 4.18 1.08
Clindamycin
phosphate
31.20 3.18 1.29 0.25 0
1200 mg in
45 minutes
Free
clindamycin
13.11 15.87 10.37 5.90 1.16
Clindamycin
phosphate
43.98 49.11 4.07 0.43 0

*                         Time A        Time B
         300 mg        0.17 hr        0.5 hr
         600 mg        0.33 hr        0.75 hr
         900 mg        0.5 hr          0.75 hr
         1200 mg       0.5 hr         0.75 hr

Absorption and Excretion in Patients With Impaired Hepatic or Renal Function

In a series of six patients with hepatic insufficiency and four patients with renal insufficiency, a single intravenous infusion of 300 mg of clindamycin phosphate was given over a period of 30 minutes. The results of these studies are summarized in Tables 9, 10, 11 and 12.

Table 9: Liver Function Tests in Patients with Impaired Liver Function
Patient
Number
Total Serum
Bilirubin
SGOT
(K units)
SGPT
(K units)
Alkaline
Phosphatase
LDH
1 7.0 150 - 150 180
2 6.6 155 74 110 -
3 8.0 35 - 50 100
4 1.6 135 - 235 -
5 > 10 2200 - 130 340
6 > 10 240 - 185 160
Table 10: Serum Levels of Free Clindamycin in mcg/mL in Patients with Hepatic Insufficiency, 300 mg Clindamycin Phosphate Infused Over 30 Minutes
Patient
Number
Time After Start of Infusion in Hours Elimination Half-
life (hrs)
0.5 1.5 3 6 12 24
1 7.19 3.61 3.36 1.96 0.74 - 4.9
2 11.60 6.32 5.25 4.04 2.23 1.30 7.0
3 8.68 7.16 5.15 3.68 1.25 0.88 4.4
4 17.75 8.60 6.08 2.77 0.83 0.0 4.8
5 8.42 4.93 3.84 2.49 0.75 0.45 4.2
6 9.51 4.63 3.38 2.66 1.31 0.0 5.8
Table 11: Renal Function Tests in Patients with Impaired Renal Function
Patient Number BUN Serum Creatinine Urine Albumin Urine Sugar
1 87 3.4 2+ 3+
2 73 3.2 2+ trace
3 78 6.4 4+ 0
4 59 1.4 0 0
Table 12: Serum Levels of Free Clindamycin in mcg/mL in Patients with Impaired Renal Function After 300 mg Clindamycin Phosphate Infused Over 30 Minutes
Patient
Number
Time After Start of Infusion in Hours Elimination Half-
life (hrs)
0.5 1.5 3 6 12 24
1 12.07 7.35 5.26 2.30 1.08 0.0 3.0
2 12.00 4.15 3.36 1.90 0.66 0.42 3.6
3 15.25 10.63 7.52 5.80 - 1.41 5.6
4 11.26 7.29 3.39 1.60 0.0 0.0 1.7

The mean elimination half-time for normal healthy men given 300 mg of clindamycin phosphate in a 10 minute infusion was 2.5 hours. The six patients with impaired liver function had a mean elimination half-time of 4.5 hours and those with impaired renal function a mean elimination halftime of 3.0 hours.

Tissue Penetration

Table 13 records tissue and body fluid levels of clindamycin base following administration of clindamycin phosphate. Clindamycin does not cross the blood-brain barrier even in the presence of inflamed meninges.

Table 13: Clindamycin Concentrations in Tissues and Fluids
Specimen Dosage of Clindamycin Phosphate Tissue or Fluid Level
Bone i.m. 300 mg every 8 hours 6.4 mcg/g
Bone i.m. 600 mg every 8 hours 1.44 mcg/g
Bone i.v. 600 mg every 8 hours 0.75 mcg/g
Bone Marrow i.m. 600 mg every 8 hours 10.83 mcg/g
Bile i.v. 300 mg every 6 hours 2.70 mcg/g
Synovial Fluid i.m. 300 mg every 8 hours 4.87 mcg/mL
Synovial Fluid i.m. 150 mg every 12 hours 15.6 mcg/mL
Pleural Fluid i.v. 450 mg every 8 hours 3.65 mcg/mL

Toxicology

Acute Toxicity

The results of LD50 studies are shown in Table 14:

Table 14: LD50 Results
Species Route LD50 (mg/kg)
Adult Mouse i.p. 1145
Adult Mouse i.v. 855
Adult Rat s.c. > 2000
Adult Rat p.o. 1832
Newborn Rat s.c. 179

Tables 15 and 16 summarize toxicity and teratology studies. Table 17 summarizes human studies.

Mutagenicity

Clindamycin phosphate did not show evidence of mutagenicity when tested in the Ames Assay (Salmonella/Microsome Test) or the Micronucleus Test.

Carcinogenesis

Long term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential.

Table 15: Toxicity Studies
Type of
Study
Species Route Dose
mg/kg/day
Duration Conclusions
Tolerance Rabbit
N = 3
i.m. 100, 200,
300 mg
single
dose
Slight to moderate local irritation
Tolerance Rat
N = 10
s.c. 120 6 days Local evidence of multiple epidermal breakdown with scab formation over the injection site was present in most rats. No systemic evidence of drug effect was detected at necropsy. Organ weights were not significantly different from control animals and likewise no significant deviations of hematologic data were noted among treated animals.
Tolerance Dog
N = 3
i.m. 60 6 days These doses were well tolerated by the dogs. Serum transaminase values were elevated terminally with SGOT values increasing in advance of SGPT values, suggesting that the source of these changes was the injected muscles. No other evidence of treatmentrelated changes was noted in terminal hemograms, blood chemistry values and urinalyses. Gross pathological changes were confined to the injection sites where there were signs of slight hemorrhage and edema.
Subacute
Toxicity
Rat
N = 10
s.c. 30. 60. 90 1 month No drug-related systemic effects were observed. Local inflammatory changes were seen at all three dose levels with focal necrosis of the subcutaneous tissues and overlying epidermis seen in the 60 and 90 mg/kg groups.
Subacute
Toxicity
Dog
N = 9
i.m. 30. 60. 90 1 month Under the conditions of this study, clindamycin phosphate was found to be mildly to moderately irritating. Elevations of SGOT and SGPT were noted in these dogs and were thought to be due to muscle damage caused by the injections. Other blood evaluations and liver function tests were in the normal range. A slight dose-related increase in liver weight was indicated on the basis of per cent of body weight, but no morphologic evidence of drug effect on the liver was obtained.
Subacute
Toxicity
Dog
N = 8
i.v. 60. 120 1 month No drug related effects were observed in any of the animals during or after the intravenous administrations. In particular, there was no evidence of drug-induced hemolysis or drug-related changes in the cephalic veins on both gross and microscopic examination.
Table 16: Teratology Studies
Species Route Dose
mg/kg/day
Duration Conclusions
Rat s.c. 0, 100, 180 gestation
days
6 - 15
Not teratogenic.
Mouse s.c.
2 strains
100, 180 gestation
days
6 - 15
A low incidence of cleft palate occurred in one strain in the initial experiment and as a result, the study was repeated twice with no abnormalities noted. The study in the second strain of mice was completely within normal limits.
Rat p.o. 100, 300 -- No biologically significant effect on the reproductive parameters studied was noted. Pups from treated females were slightly lighter at birth and weaning but post-natal survival was not affected by this slight weight reduction. None of the pups which were dead at birth, died before weaning, or were sacrificed at weaning, exhibited significant morphologic abnormalities.
Table 17: Human Tolerance Studies
N Route Dose Duration Conclusions
8 i.m. 300 mg clindamycin phosphate single dose Subjectively, one patient had mild pain, four had moderate pain and two had marked pain which did not occur immediately, but reached its maximum at 10 to 30 minutes after injection and subsided to a mild ache 30 to 60 minutes later. Clinical laboratory findings were all normal.
8 i.m. 600 mg clindamycin phosphate single dose Only three patients had short-lived moderate pain 30 minutes after injection.
24 i.m. Group 1 (8 patients): 300 mg clindamycin phosphate every 8 hr
(total 43
injections)
One volunteer in each of the clindamycin phosphate and Lincocin group was removed from the study after 41 injections due to local intolerance. One volunteer from sodium chloride group left on day 5 (after 15 injections) complaining that the injections were too painful. Three Lincocin volunteers were dropped from the study on day 8 (after 24 injections); one due to local discomfort and a suspected viral illness; one due to a rash and one because of headache and tinnitus. In general, in these small groups, clindamycin phosphate was as well tolerated as Lincocin. There was no necrosis in any case. Pain, tenderness, swelling and induration were typically mild. Two clindamycin phosphate-treated volunteers developed mild cases of loose stools, lasting two to ten days during treatment. Audiometric examinations showed no change from pre-treatment examinations. Clinical laboratory findings did not indicate any drug-induced toxicity. A marked rise in creatinine phosphokinase was seen in both the clindamycin phosphate and Lincocin groups. SGOT also rose above normal in the clindamycin group, but not in the Lincocin group. SGPT findings remained within normal range in all groups. These changes are consistent with changes due to muscle irritation and not attributed to liver damage.
Group 2: (8 patients): 2 mL of sodium chloride injection, USP
Group 3: (8 patients): 600 mg Lincocin sterile solution
20 i.v. Dosing Schedule five days Tolerance observations included blood pressure, pulse, respiratory rate and lead II electrocardiographic monitoring prior to, every 5 minutes during and at the end of each infusion. A 12 lead electrocardiographic tracing was done prior to treatment and after the 12th infusion. Audiograms were performed prior to treatment, within 48 hours after and 90 days after the 12th infusion. Subjects were watched closely for signs of local intolerance during each infusion period. Prior to the 1st, 5th, 9th and 4 hours after the 12th infusion, blood and urine samples were obtained for the following clinical laboratory determinations: complete blood count (CBC); complete urinalysis; serum glutamic oxalacetic transaminase (SGOT); serum alkaline phosphatase; serum creatinine; total, direct and indirect bilirubin; urine bilirubin; and serum haptoglobin. None of the tolerance data indicated any clinically significant side effects from the intravenous infusion of clindamycin phosphate.
Subject
Nos.
Treatment
Group
Dose
(mg)
Infusion
Regimen
Infusion
Rate
Total
Daily
Dose
1 - 6 A 300 4 doses
bid
4 doses
tid
4 doses
qid
30
mg/min
for 10
minutes
600
900
1200
7 - 12 B 600* 4 doses
bid
4 doses
tid
4 doses
qid
30
mg/min
for 20
minutes
1200
1800
2400
13 - 16 C 900 4 doses
bid
4 doses
tid
4 doses
qid
30
mg/min
for 30
minutes
1800
2700
3600
17 - 20 D 1200 4 doses
bid
4 doses
tid
4 doses
qid
26.7
mg/min
for 45
minutes
2400
3600
4800

*Subject 7 and 8 received 1200 mg in 20 minutes on infusion #1