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
Geocillin Pharmacology, Pharmacokinetics, Studies, Metabolism - Carbenicillin Indanyl Sodium
Geocillin Pharmacology, Pharmacokinetics, Studies, Metabolism - Carbenicillin Indanyl Sodium
CLINICAL PHARMACOLOGY
Free carbenicillin is the predominant pharmacologically active fraction
of Geocillin. Carbenicillin exerts its antibacterial activity by interference
with final cell wall synthesis of susceptible bacteria.
Geocillin is acid stable, and rapidly absorbed from the small intestine
following oral administration. It provides relatively low plasma concentrations
of antibiotic and is primarily excreted in the urine. After absorption,
Geocillin is rapidly converted to carbenicillin by hydrolysis of the ester
linkage. Following ingestion of a single 500 mg tablet of Geocillin, a
peak carbenicillin plasma concentration of approximately 6.5 mcg/ml is
reached in 1 hour. About 30% of this dose is excreted in the urine unchanged
within 12 hours, with another 6% excreted over the next 12 hours.
In a multiple dose study utilizing volunteers with normal renal function,
the following mean urine and serum levels of carbenicillin were achieved:
| DRUG |
DOSE |
Mean Urine Concentration of
Carbenicillin µg/ml
Hours After Initial Dose
|
| 0-3 |
3-6 |
6-24 |
| Geocillin |
1 tablet
q.6 hr |
1130 |
352 |
292 |
| Geocillin |
2 tablets
q.6 hr |
1428 |
789 |
809 |
| Mean serum concentrations of carbenicillin
in this study for these dosages are: |
| DRUG |
DOSE |
Mean Serum Concentration µg/ml
Hours After Intial Dose
|
| 1/2 |
1 |
2 |
4 |
6 |
24 |
25 |
26 |
28 |
| Geocillin |
1 tablet
q.6 hr |
5. 1 |
6. 5 |
3.2 |
1. 9 |
0.0 |
0.4 |
8.8 |
5. 4 |
0. 4 |
| Geocillin |
2 tablets
q.6 hr |
6.1 |
9. 6 |
7. 9 |
2. 6 |
0.4 |
0.8 |
13. 2 |
12.8 |
3.8 |
Microbiology
The antibacterial activity of Geocillin is due to its rapid conversion
to carbenicillin by hydrolysis after absorption. Though Geocillin provides
substantial in vitro activity against a variety of both gram-positive
and gram-negative microorganisms, the most important aspect of its profile
is in its antipseudomonal and antiproteal activity. Because of the high
urine levels obtained following administration, Geocillin has demonstrated
clinical efficacy in urinary infections due to susceptible strains of:
| Escherichia coli |
Pseudomonas species |
| Proteus mirabilis |
Providencia rettgeri |
| Proteus vulgaris |
(formerly Proteus rettgeri) |
| Morganella morganii |
Enterobacter species |
| (formerly Proteus morganii) |
Enterococci (S. faecalis) |
In addition, in vitro data, not substantiated by clinical studies,
indicate the following pathogens to be usually susceptible to Geocillin:
| Staphylococcus species |
|
| (nonpenicillinase producing) |
|
| Streptococcus species |
|
Resistance
Most Klebsiella species are usually resistant to the action of
Geocillin. Some strains of Pseudomonas species have developed resistance
to carbenicillin.
Susceptibility Testing
Geopen (carbenicillin disodium) Susceptibility Powder or 100 µg. Geopen
Susceptibility Discs may be used to determine microbial susceptibility
to Geocillin using one of the following standard methods recommended by
the National Committee for Clinical Laboratory Standards:
M2-A3, "Performance Standards for Antimicrobial Disk Susceptibility Tests"
M7-A, "Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria
that Grow Aerobically"
M11-A, "Reference Agar Dilution Procedure for Antimicrobial Susceptibility
Testing of Anaerobic Bacteria"
M17-P, "Alternative Methods for Antimicrobial Susceptibility Testing of
Anaerobic Bacteria"
Tests should be interpreted by the following criteria:
| Organisms |
Disk Diffusion
Zone diameter (mm)
|
| Suscept. |
Intermed. |
Resist. |
| Enterobacter |
³ 23 |
18- 22 |
£17 |
| Pseudomonas sp. |
³17 |
14- 16 |
£13 |
| Organisms |
Dilution
MIC (µg/ ml)
|
| Suscept. |
Moderately Suscept. |
Resist. |
| Enterobacter |
£16 |
32 |
³ 64 |
| Pseudomonas sp. |
£128 |
— |
³156 |
Interpretations of susceptible, intermediate, and resistant correlate
zone size diameters with MIC values. A laboratory report of "susceptible"
indicates that the suspected causative microorganism most likely will
respond to therapy with carbenicillin. A laboratory report of "resistant"
indicates that the infecting microorganism most likely will not respond
to therapy. A laboratory report of "moderately susceptible" indicates
that the microorganism is most likely susceptible if a high dosage of
carbenicillin is used, or if the infection is such that high levels of
carbenicillin may be attained as in urine. A report of "intermediate"
using the disk diffusion method may be considered an equivocal result,
and dilution tests may be indicated.
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