Current Topic: Review

Vol. 13. No. 10

839

Eur. J. Clin. Microbiol. Infect. Dis., October 1994, p. 83%845

0934-9723/94/10 0839-07 $3.00/0

Comparative Microbiological Activity and Pharmacokinetics

of Cefprozil
R. Wise

In vitro studies on the activity of cefprozii have been conducted in Europe and North
America. Against gram-negative bacilli, cefprozil and cefaclor are at least two to four
times more active than cephalexin. Cefixime is more active against these organisms.
Against gram-positive cocci, cefprozil is at least two to four times more active than cefaclor and cephalexin; cefixime has limited gram-positive activity, and is particularly
inactive against staphylococci (MIC90 32 rag/i). Cefprozil is highly active against
Streptococcus pneumoniae (unlike cefixime). Those strains of this genus that display
intermediate resistance to pneumococci are more susceptible to cefprozil than cefacior. Neisseria species and Moraxella catarrhalis are susceptible to cefprozil (MIC90
0.06 and 1 rag/I). [3-1actamase-producing strains ofHaemophilus influenzae appear to
be susceptible to cefprozii, as the reported MIC90 is 2-4 mg/l. Enterococci, Pseudomonas aeruginosa, and those strains of the Enterobacteriaceae that commonly
possess a chromosomal cephalosporinase (e.g., Providencia, Morganella and Enterobacter) are generally considered to be resistant to cefprozil as well as to other oral
cephalosporins. Cefprozil appears to display enhanced stability to the commonly encountered Tem-1 and SHV-1 plasmid-mediated ~.iactamases, as found in
Haemophilus influenzae, Neisseria gonorrhoeae and the Enterobacteriaceae. Cefprozil is rapidly absorbed, reaching a maximum concentration 0.9 to 1.2 h post-dose.
Following oral doses of 250 and 500 mg, the Cmax is 6.2 and 10.0 rag/! respectively.
Serum half-lives are generally reported as between 1.2 and 1.4 h, and urine recovery is
high, 57-70 %. Ingestion of fired has no significant effect on cefprozil pharmacokinetics, but does reduce the serum levels of cefaclor. Studies in severe renal dysfunction
suggest that only when the creatinine clearance is under 30 ml/min (when the half-life
exceeds 5 h) is there a need for a reduction in the dosage of cefprozil by 50 % or an increase of the dosage interval. Children (over 2 months of age) have very similar pharmacokinetics, the only difference being a slightly shorter cefprozil half-life (ca. 1.0 h).
Studies in the elderly suggest that age, per se, does not need an alteration in dosing,
The tissue penetration of cefprozil is similar to that of other ~-iactams and the blisterfluid model demonstrates that 80 % penetration is found in an inflammatory exudate.

Since its discovery in 1953, the cephalosporin

molecule has proved to be highly versatile, and
Over 100 semisynthetic cephalosporins have been
developed, the majority of these being parenteral. The first oral compound, cephalexin, although still widely used, has relatively poor activity against some respiratory and urinary pathogens. Similarly, the other early compounds, such
as cefaclor and cephalexin, display modest activity or poor pharmacokinetics. In the more recent

Department of Medical Microbiology,DudleyRoad Hospital,

Dudley Road, Birmingham B18 7QH, UK,

past, oral cephalosporins have developed along

two lines. Firstly, as pro-drugs, such as cefuroxime
axetil and cefpodoxime proxetil, and secondly as
compounds that remain unchanged following ingestion and absorption, such as cefixime, and now
cefprozil. Increasing 13-1actamase resistance
amongst gram-negative bacilli has motivated the
development of more [Mactamase-stable agents
and compounds with more favorable pharmacokinetics, requiring less frequent administration
and hence improved patient compliance. The earliest oral cephalosporin, cephalexin, displayed
poor activity against Haernophilus influenzae, the
MIC90 being 16 mg/l (1) and the maximum serum

840

Eur. J. Clin. Microbiol. Infect, Dis.

concentrations being only 18 mg/1 after the usual

dose (500 mg). Streptococcus pneumoniae (unless
penicillin-resistant) is inhibited by low concentrations of all the earlier oral cephalosporins.
Against Staphylococcus aureus the earlier agents
have only modest activity, and more recent additions such as cefixime are much less active
(MIC90 12.5 mg/l compared with cephalexin
6.25 rag/l) (2). The earlier agents, such as cephalexin and cefaclor, are not particularly stable to
the common TEM-1 13-1actamase, although the
more recent additions such as cefixime and cefpodoxime, are not so readily hydrolyzed (2).
The earlier oral cephalosporins (including cefuroxime axetil) have elimination times of under
1.25 h, which suggests that they should be given
three or four times a day. Cefpodoxime and cefixime have half-lives of 2.5 and 3.3 h, hence less
frequent administration is reasonable (3). There
is a need for an oral agent that combines good activity against both respiratory pathogens and
staphylococci, is stable to the commonly occurring plasmid mediated [3-1actamase, and has pharmacokinetics compatible with one or two daily
doses. This review compares the in vitro activity
and pharmacokinetics of the newer oral cephalosporin cefprozil with those of other [Mactams that
are commonly employed in the treatment of community-acquired infections.

cloacae (data not shown) - are resistant to cefprozil and the other cephalosporins, with the
possible exception of cefixime. Pseudomonas
aeruginosa and other Pseudomonas species, together with Xanthomonas maltophilia, are resistant to all the oral cephalosporins (7).
Amongst the enteric pathogens, Shigella species
are reported as variably susceptible (MIC90 232 mg/1) as are Salmonella species and Yersinia
en terocolitica.
The respiratory pathogens Haemophilus influenzae and Moraxella catarrhalis are" susceptible to cefprozil and cefaclor; cephalexin is about
four times less active. Those strains of Haemophilus influenzae that possessed a [Mactamase
were resistant to amoxicillin (mode MIC 4 mg/1),
yet susceptible to cefprozil (mode MIC i mg/1),
but are less susceptible than the 13-1actamasenegative strains (mode MIC 0.004 mg/1). Streptococcus pneumoniae is highly susceptible to all the
I]-lactams, with the exception of cefixime and
cephalexin, which are markedly less active. Cefaclot was consistently two times less active than
cefprozil.

BO

~
gl

-~
Microbiological

Activity

A large number of in vitro studies have been performed in North America, Europe and Japan (19). In a study we have undertaken, the activity of
cefprozil was compared with that of other [Mactams. An inoculum of 104 CFU was used, and
standard methodology employed (10). The results are shown in Table 1. In general, cefprozil,
cefuroxime and cefaclor have a similar potency
against the commonly encountered Enterobacteriaceae; cephalexin tends to be two to four times
less active, and cefixime markedly more active.
Amoxicillin displays bimodal activity, presumably reflecting the lack of activity against the
commonly encountered plasmid mediated l~-lactamases in these genera. The activity of amoxicillin-clavulanate (expressed as the MIC of amoxicillin) was similar to that of cefprozil. Those
strains of Enterobacteriaceae that commonly express a chromosomal lactamase - such as Morganella morganii, Proteus vulgaris, Providencia
stuartii, Serratia marcescens and Enterobacter

70

60

so
4o 3o
20

10

7r ,_ H

0.03 0.06 0,12 0.25 0,5

16

32 >32

16

32 >32

MIC mgll

so
70

60
u~

50
40
30
20
10
0
0,03 0,06 0,12 0,25 0,5

MIC mgtl
[ r ' ] Cefprozi,

I-"~ Cefaclor I

Figure 1: (A) Activityof cefproziI and cefaclor vs. penicillin-sensitive pneumococci (MIC < 0.12 mg/1). Number
of isolates = 18I. (B) Activityof cefprozil and cefaclorvs.
relatively penicillin-resistant pneumococci (MIC 0.121.0 rag/l). Number of isolates = 160 (ref. 11).

V o l . 13, 1994

841

Table 1: In vitro activity of cefprozil (mg/l) compared to other I~-lactams.

Organism (No.)

Antibiotic

Escherichia coa (50)

Cefprozil
Cefixime

Cefuro~me
Cefaclor
Cephalexm
Amoxicillin
AmoxicUtin-CA

Klebsiella species (48)

Cefprozil
Cefixime
Cefuroxlme
Cefaclor
Cephalexm

Amoxicillin
Amoxicillin-CA

Proteus mirabilis (47)

MIC50

0.004 - 4
0.O6 -64
0.5 -16

l
0.03
1
0.5
4
64
1

32
0.12
16
t6
32
> 128
16

0.25 - > t28

0.004 - 1
0.24 - > 128
0.5 - 128
2 - I28
0.12 - > 128
1 - > 128
1 - > 128
0.004 - 0.06
0.25 - 16

64
0.008
32
64
64
128
4

> 128
0.015
> 128
128
> 128
> t28
8

I - > 128
0.004 - 0.03
0,5 - > 128
2 - > 128
32 - > 128
0.12 - > 128
0.5 - 32

32
0,06
16

> 128
0.12
128

0.5
0.004
0.12
8
4
4
0.25

Cefprozil
Cefixime
Cefuroxime
Cefaclor
Cephalexm
Amoxicillin
Amoxicilfin-CA

Morganella morganii (23)

Cefprozil
Cefixime
Cefuroxime
Cefaclor
Cephalexm

> I28

> 128

Amoxicillin-CA

> 128
128
64

> 128
> 128
128

Cefprozit
Cefixime
Cefuroxime
Cefaclor
Cephalexm
Amoxicillin

t28
&25
> 128
> 128
> 128
4

128
8
> 128
> 128
> 128
128

Amoxicillin-CA
Cefprozit
Cefixime
Cefuroxime
Cefaclor
Cephalexin
Amoxicillin
Amoxicillin-CA

0.5 - > 128

0.5 - 32

4
0.008
2
2
8
1
2

1
0.008
0.5
1
8
0.25

Proteus vulgaris (20)

Amoxieillin

0.25 - 3 2

0,25
4
2
4
> I28
8

0.5

Providencia stuartii U 7)

Range

0,06
2
1
4
4
4

Cefprozi|
Cefixime
Cefuroxtme
Cefaclor
Cephalexm
Amoxicillin
Amoxicillin-CA

Serr atia marcescens (9)

MIC90

4
32
0,0]5
1
32
32
128
64

128
> 128
0.25
16
64
128
> 128
128

0.25 - > 128

0.5 - 32

- > 128
-128
- 128
- > 128
- > 128
- > 128
- > 128

4 - > 128
0.12 - 128
16 - > 128
16 - > 128
32 - > 128
0.12 - > 128
8 - 128
8
0.015
0.25
0.5
32
32
4

- > 128
- > 128
- > 128
- > 128
- > 128
- > 128
- 128

842

E u r . J. C l i n . M i c r o b i o l . I n f e c t . D i s .

Table 1: continued.
Organism (No.)

Antibiotic

Haemophilius infiuenzae (34)

Cefprozil
Cefixime
Cefuroxime
Cefaclor
Cephalexin
Amoxicillin
Amoxicillin-CA

0.004
0.004
0,5
0,5
0.12
0.5
0.25

2
0.06
1
2
8
4
0.5

0.008
0.008
0.008
0.12
0.5
0.06
0.06

- 4
- 0.06
- 2
-4
-16
- 8
- 1

Moraxella catarrhalis (28)

Cefprozil
Cefixime
Cefuroxime
Cefaclor
Cephalexin
Amoxicillin
Amoxicillin-CA

0.004
0.004
1
0.06
0.12
0.25
0.015

1
0,12
2
1
4
4
0.12

0.008
0,008
0.008
0.06
0,12
0.015
0.015

- 2
-0.5
-4
- 1
-8
- 8
-0.25

Neisseria meningitidis (10)

Cefprozil
Cefixime
Cefuroxime
Cefaclor
Cephalexin
Amoxicillin
Amoxicillin-CA

0.004
0.004
0.015
0.06
0.12
0,03
0.015

0.06
0.004
0.06
0.06
0.25
0.06
0.03

0.008
0.004
0.015
0.06
0.12
0.03
0.015

- 0.25
- 0.06
-0,12
- 0.12
-2
-0.12
-0.06

Streptococcus pneumoniae (20)

Cefprozil
Cefixime
Cefuroxime
Cefaclor
Cephalexin
Amoxicillin
Amoxicillin-CA

0,06
0.12
0.015
0.25
2
0.015
0.015

0.25
1
0.12
O, 5
2
0.03
0.03

0.06
0.06
0.015
0.12

- 1
-2
-0.12
- 1

Cefprozil
Cefixime
Cefuroxime
Cefaclor
Cephalexin
Amoxicillin
Amoxicillin-CA

0.25
8
0.5
2
4
0.5
0.25

2
16
1
4
32
0.5
0,5

0,12 - 2
2 - > 128
0.25 - 8
0.5 - 3 2

Cefprozil
Cefixime
Cefuroxime
Cefaclor
Cephalexin
Amoxicillin
Amoxicillin-CA

0.25
4
0,25
0.5
2
0.25
0.12

2
32
4
8
32
2
0.5

0.12 - 2
0.25
0.5
0.5
0.25
0.06

- 4
-8
- 32
- 4
- 0.5

0.25
32
1
2
4
0,25
0.25

1
64
4
4
8
0.5
0.5

0.25
2
0.12
0.5
2
0,25
0.12

- 32
- > 128
- > 128
- 64
-128
- 16
- 8

(including ampiciltin-resistant
strains)

Staphylococcus aureus (30)

Staphylococcus epidermidis (20)

Staphylococcus saprophyticus (20) Cefprozil

Cefixime
Cefuroxime
Cefaclor
Cephalexin
Amoxicillin
Amoxicillin-CA
Amoxicillin-CA = amoxicillin-clavulanate.

MIC50

MIC90

Range

0.015 - 0,25
0.015 -0.25

0.25 - 8
0,12 - 8

Vol. 13, 1994

843

The activity of cefprozil and cefaclor against

pneumococci less susceptible to penicillin (MIC
0.12-1.0 mgfl) has been studied (data on file). In
Figure 1, the activity of these two agents against
penicillin-susceptible (MIC < 0.12 rag/l) and relatively resistant strains (MIC 0.12-1.0 mg/l) is
shown. It can be seen that cefprozil is two to four
times more active than cefaclor against both
populations of pneumococci.

Staphylococcus aureus (methicillin-susceptible)

is two times more susceptible to cefprozil than to
cefaclor; cefixime and cephalexin were eight to 16
times less active. Similar differences were seen for
the Staphylococcus epidermidis and Staphylococcus saprophyticus tested.
Lancefield Group A and B streptococci are susceptible to cefprozil (MIC90 0.03 and 0.12 mgfl
respectively) Enterococcus faecalis tends to be
more susceptible to cefprozil (MIC90 8 mg/l) than
to other oral cephalosporins. Bacteroides fragilis
is not susceptible to any oral cephalosporin, but
Bacteroides rnelaninogenicus is moderately susceptible, with a cefprozil MIC of 4 mg/1 (7). Clostridium perfringens tends to be susceptible
(MIC90 0.5 rag/l); some strains of CIostridium
difficile are susceptible (MIC90 2 mg/l), and anaerobic cocci are also susceptible (MIC901 mg/1).
Like other cephalosporins, cefprozil is bactericidal at concentrations similar to or slightly greater
than the MIC (data on file).
There is conflicting information on the 13-1actamase stability of cefprozil. Some information
suggests that it is as stable as cefaclor to the commonly encountered plasmid-mediated 13-tactamases, such as TEM-1 and SHV-1 (1-7), although some French data (8) suggest poor stability to these enzymes and the less common extended-spectrum [3-1actamases. The relative sta-

bility to hydrolysis in comparison to cephaloridine or penicillin G is shown in Table 2. In all the

examples shown, cefprozil is more stable to these
enzymes than cefaclor (data on file).
Of practical value to those working in the laboratory is the stability of an antimicrobial agent in solution. In a study of cefprozil, cefaclor, and
cephalexin in human serum at p H 6. 8 (9), there
was about a 20 % loss of activity of cefaclor over
2 h; the loss of a similar amount of cefprozil occurred over 8 h, and cephalexin in more than 24 h.
Studies conducted by Bristol-Myers Squibb (data
on file) suggest a breakpoint of over 8 mg/1 being
considered resistant. This is now the NCCLS
guideline (3), and is the same breakpoint as that
for cefaclor and cephalexin. I consider this might
be too high for some in Europe, and suggest that a
more conservative 2-4 mg/l for respiratory infections would be more appropriate (11).

Human Pharmacokinetics
Cefprozil consists of both cis and trans isomers in
a 9:1 ratio, and their pharmacokinetics are very
similar. Cefprozil is rapidly absorbed following
oral administration, reaching a maximum concentration in serum of 0.9 to 1.2 h post-dose. The
mean maximum serum concentrations (Cmax)
are 6.2 mg/l after 250 mg and 10 mg/l after 500 mg
(the two doses commonly used in clinical practice) (data on file). Serum elimination half-lives
vary from 1.2 to 1.4 h in volunteers, and the urinary recovery from 56 % to 70 % of the administered dose. Cefprozil exhibits linear pharmacokinetics between doses of 250 and 1000 rag. As
might be expected with an agent with a half-life of
1.4 h, no accumulation occurs on a twice-daily

Table 2: Beta-lactamase stability of new oral eepha[osporins: relative hydrolysis rates. Standards: penicillin G and
cephaloridine. Lower hydrolysisrate values indicate greater stability against hydrolyzingenzymes.
Enzyme

Escherichia coli ITEM- 1

Escherichia coti I TEM-2

Cefprozil
1
20
1.2

Cefaclor

Cephalexin

2.1
53

0.1
<6

2.1

0.1

Cefixime

Penicillin
100

100
< 0.1

100

Klebsiellapneurnoniae t SHV-1

21

105

Escherichia coli / OXA-1

< 0.2

17

0.4

< 0.1

100

02

0.2

< 0.1

100

Staphylococcus aureus I Type V

Cephaloridine

15
100

0.2

844

Eur. J. Clin. Microbiol. Infect. Dis.

iI~250mg

250rag Cefprozll

Cefaclor

g6

"4=

Time (houre)

Time

(hours)

Figure 2: Mean plasma concentration vs. time profiles of

cefprozil and cefaclor under fed (m) and under fasting
conditions (O). Adapted from Barbhaiya et al. (ref. 13).
10

per se, does not need any alteration to the dosing

regimen (16). Children aged eight months to eight
years received a single dose of either 15 mg/kg or
30 mg/kg cefprozil. The mean maximum serum
levels were 12 and 18 mg/l, respectively. The mean
elimination half-life in these children was 1.6 h
and 2.1 h, respectively.
The effect of eight days of cefprozil 500 mg b.i.d.
on the intestinal microflora has been studied (11).
The ecological impact included a moderate
decrease in the numbers of Enterobacteriaceae
and a slight increase in the numbers of'enterococci, staphylococci and Bacteroides species. The
numbers of all bacterial species normalized four
days after the end of administration. It is thought
that the relatively limited effect of cefprozil upon
the gastrointestinal flora is related to its high level
of absorption after oral administration, so that intestinal exposure is relatively low.

I
I
0

0.1

0.0t

I
2

I
4

!
6

I
8

Tissue Distribution
10

Time (Hours)

Figure 3:. Plasma (m) and blister-fluid (O) concentrations

of cefprozil over time in hours. Adapted from Nye et al.,
(ref. 18).
dosing schedule (11). Ingestion of food that influences cefaclor has no statistically significant effect on the absorption or elimination of cefprozil
(12) (Figure 2). Co-administration of an antacid
(aluminum hydroxide) does not affect the absorption of cefprozil (13).
Studies in renal failure show, as might be expected, slower elimination with increasing impairment of renal function (14). Similarly, the
area under the plasma concentration-time curve
increased. A reduction in dose was recommended
by these workers when the creatinine clearance
fell below 30 ml/min. Haemodialysis decreases
the half-life of cefprozil, and haemodialysis clearance was about 87 ml/min; a three-hour dialysis
session will remove 55 % of cefprozit from the
body, and after haemodialysis, a further dose of
cefprozil is necessary.
A study in hepatic impairment (15) showed that
the pharmacokinetics of cefprozil are not significantly affected by liver dysfunction. A study in
elderly patients (61-80 years) who received a
single 1000 mg dose of cefprozil showed slightly
slower elimination than with a younger group; age

In a volunteer study, we have investigated the

penetration of cefprozil into a chemically induced
inflammatory exudate (17). The agent penetrates
rapidly into the inflammatory exudate and 80 %
penetration was found (Figure 3). These data suggest that the antibacterial effect in inflammatory
fluid will be more protracted than in serum, and
that concentrations sufficient to inhibit Haemophilus influenzae and Staphylococcus aureus are
present for around 6 h after a single dose, and
Streptococcus pyogenes and Streptococcus pneumoniae would be inhibited for over 12 to 15 h.
The penetration of cefprozil into tonsillar and adenoid tissue was studied in children receiving
single doses of 7.5 mg/kg or 20 mg/kg (data on file).
The concentrations of cefprozil in these tissues
were equivalent to those found in plasma 1-4 h
after administration of the dose, and exceeded the
MIC for Streptococcus pyogenes at least 25-fold.
Conclusions

Cefprozil has an antimicrobial spectrum of activity encompassing the bacterial pathogens that are
commonly encountered in the community and
cause infections of the respiratory tract, urinary
tract and those of skin and related structures. The
pharmacokinetics are those of a well-absorbed [3lactam that has little impact on the body' s microflora.

Voi. 13,1994

References

1~ Chin N-X, Neu HC: Comparative antibacterial activity

of a new oral cephalosporin, BMY 28100. Antimicrobial Agents and Chemotherapy 1987, 31: 480--483.
2, Hiraoka M, Masuyoshi S, Tomatsu K: In vitro activity
and 13-1actamase stability of the oral cephalosporin
BMY 28100. European Journal of Clinical Microbiology 1987, 6: 559-563.
3, Jones RN, Bart3, AL: BMY 28100, a new oral cephalosporin: antimicrobial activity against nearly 7000 recent
clinical isolates. Diagnostic Microbiology and Infectious Diseases 1988, 9: 11-26.
4. Leitner E, Pursiano PA, Buck RE: BMY 28100, a
new oral cephalosporin. Antimicrobial Agents and
Chemotherapy 1987, 31: 238-243.
5. Kayser F: Comparative antibacterial activity of a new
oral cephalosporin BMY 28100. European Journal of
Clinical Microbiology 1987, 6: 309-312.
6. Steele J, Edwards B, Rissling J: In vitro activity of
BMY 28100, a new oral cephalosporin. European Journal of Clinical Microbiology 1987, 6:111-113.
7. Thornsberry C: Review of the in vitro antibacterial
activity of cefprozil, a new oral cephalosporin. Clinical
Infectious Diseases 1992, 14: Supplement 2: 189-194.
8. Kitzis MD, Liassine N, Ferre B, Gutman L, Acar JF,
Goldstein F: In vitro activities of 15 oral [Mactams
against Klebsiellapneumoniaeharboring new extended
spectrum ~-lactamases. Antimicrobial Agents and
Chemotherapy 1990, 34: 1783-1786.
9. Tomatsu K, Ando S, Masuyoshi S, Kondo S, Kawaguchi H: In vitro and in vivo evaluation of BMY 28100,
a new oral eephalosporin. Journal of Antibiotics 1987,
40: 1175-1183.

845

10. Jolly A, Andrews JM, Brenwald N, Wise R: The in

vitro activity of a new highly active quinolone, DU6859a, Journal of Antimicrobial Chemotherapy 1993,
32: 757-763.
11. Lode H, Muller C, Borner K, Nord C-E, Koeppe P:
Multi-dose pharmacokinetics of cefprozil and its effects on intestinal flora of volunteers. Antimicrobial
Agents and Chemotherapy 1992, 36:- 144-149.
12. Barbhaiya RH, Shukla UA, Gleason CR, Shuya WC,
Pittman KA: Comparison of the effects of food on
the pharmacokinetics of cefprozil and cefaclor. Antimicrobial Agents and Chemotherapy 1990, 34: 12101213.
13. Shyu WC, Wilber RB, Pittman KA, Barbhaiya RH:
Effect of antacid on the bioavailability of cefprozil.
Antimicrobial Agents and Chemotherapy 1992, 36:
962-965.
14. Shyu WC, Pittman KA, Wilber RB, Matzke GR, Barbhaiya RH: Pharmacokinetics of cefprozil in healthy
subjects and patients with renal impairment. Journal
of Clinical Pharmacology 1991, 31: 362-371.
15. Shyu WC, Wilber RB, Piltman KA, Garg DC, Barbhaiya RH: Pharmacokinectic of cefprozil in healthy
subjects and patients with hepatic impairment. Journal
of Clinical Pharmacology 1991, 31: 373-376.
16. Saez-Liarens X, Shyu WC, Shelton S, Kumiesz H, Nelson J: Pharmacokinetics of cefprozil in infants and
children. Antimicrobial Agents and Chemotherapy
1990, 34: 372-376.
17. Nye K, O'Neill P, Andrews JM, Wise R: Pharmacokinetics and tissue penetration of cefprozil. Journal
of Antimicrobial Chemotherapy 1990, 25: 831-835.