Burns (1984) 10, 290-299 Printed in Great Britain
The effect of some ointment bases on the
systemic absorption of tobramycin from
various wound surfaces of burned patients
Hisashi Aoyama, Akira Nishizaki, Yumiko Aoki and Yohei lzawa
Department of Burns and Plastic Surgery, Chukyo Hospital, Nagoya 457, Japan
Jun Okuda
Department of Clinical Biochemistry, Faculty of Pharmacy, Meijo University, Nagoya 468,
Japan
Summary
Three kinds of 0.2 per cent tobramycin ointment were
prepared with tobramycin and 3 ointment bases
(cream, polyethylene glycol and hydrophilic petrol-
atum), and applied to the various wound surfaces of
5 burned patients. The systemic absorptions of tobra-
mycin were compared with the values of the tentative
AUC (area under the curve of tobramycin blood level,
pg.h/ml.g) until 12 hours after the applications, by
determining tobramycin level in blood. Similar values
of AUC from the cream and polyethylene glycol oint-
ments were obtained, while that of hydrophilic petrol-
atum ointment was very low. The systemic absorption
of tobramycin from the polyethylene glycol ointment
was studied when the ointment was applied to the
wound surfaces of 7 patients with partial-thickness
bum, 9 patients with full-thickness bum and 6 patients
with bum ulcer. The mean values of the tentative
AUC of patients with partial-thickness bum, full-
-thickness-bum and bum-ulcer were found to be 0.06,
0.03 and 0.15. resoectivelv. These results showed that
cream and polyethylene glycol bases should be used
carefully as a vehicle of tobramycin ointments because
of the rapid systemic absorption of tobramycin from
human burn wounds, especially bum ulcer.
INTRODUCTION
IN bum treatment, anti-infection agents are top-
ically applied to control bum wound infections.
The systemic absorption of the drugs from prep-
arations applied to the bum wound surface is of
importance with regard to effectiveness, selec-
tivity and toxicity. The mode of penetration of
a topically applied drug through the bum wound
into the blood may be modified by altering the
compositions of the vehicle base. However,
there are only a few published reports describing
the different absorption of topically applied sil-
ver sulphadiazine sulphamylon acetate or sal-
icylate in different vehicles (Shelmire, 1960;
Stolar et al., 1960a, b; Harrison, 1972; Robb,
1981) and no data on antibiotics in the different
vehicles have been reported previously except
from Stone et al. (1968). To obtain the necessary
information for selection of an ointment base for
the antibiotic tobramycin, 3 kinds of0.2 per cent
tobramycin ointment were prepared with cream
(CR) base, polyethylene glycol (PG) base and
hydrophilic petrolatum (HP) base, and these
ointments were applied to various wound sur-
faces of burned patients. The rate of systemic
absorption of tobramycin from the 3 kinds of
ointment were studied and compared with each
other using the tobramycin level in the blood of
burned patients.
MATERIALS AND METHODS
Tobramycin ointments
Three kinds of bases were used in this study. CR
base (oil-in-water emulsion base) was kindly
Aoyama et al.: Ointment basesand tobranycin 291

Tab/e 1. Burned patients examined

Area applied Tobram ycin Tobram ycin

Body weight (% of TBSA) ointment absorption (AK) Postborn
Case Age Sex (kg) Total PB FB BU applied (g) Cream PG HP day tested

1 35 M 63 60 30 30 1200 0.07 0.07 0.03 2-4

2 77 F 39 60 50 10 1200 0.06 0.07 0.02 3-5
3 45 M 60 70 70 1400 0.07 0.05 0.03 3s
4 74 M 65 20 20 400 0.23 0.19 0.15 30-32
5 76 F 39 30 30 600 0.09 0.12 0.02 25-27

PB, Partial-thickness burn; FB, full-thickness burn; BU, burn ulcer; AUC, area under the curve of tobramycin
blood level (ug.hour/ml.g); PG, polyethylene glycol; HP, hydrophilic petrolatum.

time after application fhrs)

Fig. 1. Effect of 3 ointment bases on systemic absorption of tobramycin from bum

wound surface of case 1. Cream base (O), polyethylene glycol base (o), hydrophilic
petrolatum base (A).

supplied from Tokyo Tanabe Co. Ltd (Tokyo,
Japan). PG base was an equi-weight mixture of
PG 400 and PG 4000. HP base (water-in-oil
base) was obtained commercially. Pure tobra-
mycin was kindly supplied from Shionogi Phar-
maceutical Co. Ltd (Osaka, Japan) and was
mixed with each of the three ointment bases to
make up 0.2 per cent (w/w).
Application of tobramycin ointment
Comparative applications of three
tobram ycin ointments
To each of 3 adult male and 2 adult female
patients, weighing 39-65 kg, with burns ranging
from 20 to 70 per cent TBSA (total burn surface
area), sterile gauzes (average size: 14 x 23 cm)
with 0.2 per cent tobramycin-CR ointment (40 g
per gauze) were applied to cover the wound sur-
face of the burned patient for 12 hours on a
specified day after the bum (Table I). The doses
of tobramycin ointment were roughly calculated
from the numbers of the gauzes applied.
Blood (1 ml) was collected from the venous
catheters of patients at the specified times until
kinds of 10 or 12 hours after the application (Figs. l-5).
Twenty-four hours after the application, the
tobramycjn-CR ointment gauzes were removed
from the burned wound surface and 0.2 per
 BurnsVol. lo/No. 4

0 1 2 3 4 5 6 7 6 9 10 11 12
time after application (hrs)

Fig. 2. Effect of 3 ointment bases on the systemic absorption of tobramycin from

bum wound surface of case 2. Cream base (0) polyethylene glycol base (O),
hydrophilic petrolatum base (A).

Id
OId
0 1 2 3 4 5 6 7 6 9 10 11 12
time after application (hrs)

Fig. 3. Effect of 3 ointment bases on the systemic absorption of tobramycin from

bum wound surface of case 3. Cream base (II), polyethylene glycol base (O),
hydrophilic petrolatum base (A).
Aoyama et al.: Ointment bases and tobramycin
time after
Fig. 4.Effect of 3 ointment bases on the systemic absorption of tobramycin from
bum wound surface of case 4. Cream base (III), polyethylene glycol base (0),
hydrophilic petrolatum base (A).
cent tobramycin-PG or tobramycin-HP oint-
ment gauzes were successively applied to the
burned surface of the same patient, along with
tobramycin-CR ointment. The serum levels of
tobramycin in these blood samples were deter-
mined by enzyme immunoassay (Emit) (Brogden
et al., 1976) and the values of AUC (area under
curve of tobramycin blood level, ug.hIm1.g) of
the ointment were obtained from Figs. l-5 to
compare the systemic absorption of tobramycin
during the 12 hours in each case.
Application of tobramycin-PG ointment to the
various wound surfaces of burned patients
Tobramycin-PG ointment (0.2 per cent) pre-
pared with tobramycin and PG base was applied
to the various burned wound surfaces of 15 male
and 7 female patients (Table II). A blood sample
(1 ml) was also collected from the venous cath-
eter of each patient at the specified times until
12 hours after the drug application (Figs. 6-8).
Serum tobramycin levels were determined using
the enzyme immunoassay, and the AUC values
were obtained from Figs. 6-8 as shown in Table
II. Seven patients (5 male and 2 female) with
293
application (hrs 1
partial-thickness burns (range 30-90 per cent
TBSA), 9 patients (6 male and 3 female) with
full-thickness bums (range 30-75 per cent
TBSA) and 6 patients (4 male and 2 female) with
bum ulcers (range 20-30 per cent TBSA) were
treated with the 0.2 per cent tobramycin-PG
ointment. The applications of tobramycin-PG
ointment were carried out on a specified post-
bum day as shown in Table II.
In cases when the blood levels of tobramycin
were not determined until 12 hours after the
applications of the tobramycin ointment (Figs.
6-S), the lines were extrapolated until 12 hours
and the AUC values were calculated.
RESULTS
Comparative applications of three
tobramycin ointments
Case 7
The systemic absorption of topically applied
tobramycin was first studied on a male patient
(patient 1, age 35 years, 63 kg body weight) with
bums of 60 per cent TBSA (30 per cent partial-
thickness bum, 30 per cent full-thickness burn)
during 3 days from postbum days 2 to 4. Twelve
 294 Burns Vol. lo/No. 4

0 1 2 3 4 5 6 7 8 9 10
time after application (hrs)
Fig. 5. Effect of 3 ointment bases on the systemic absorption of tobramycin from
bum wound surface of case 5. Cream base (O), polyethylene glycol base (0),
hydrophilic petrolatum base (A).

hundred grams of 0.2 per cent tobramycin-CR,
-PG or -HP ointment was applied topically
(Table 1).
As shown in Fig. 1. tobramycin serum level
after the application of tobramycin-CR oint-
ment was found to be 5.0 &ml at 2-4 hours,
while that of tobramycin-PG ointment was 6.1
ug/ml at 2.0 hours. That oftobramycin-HP oint-
ment was 1.2 @ml at 2-O hours which is signifi-
cantly lower. From Fig. 1, AUC values for the
three applications were obtained as shown in
Table I. The AUC values forthe cream and PG
ointments were similar, while that of HP oint-
ment was very low. These values revealed that
the systemic absorptions of tobramycin from
both cream and PG ointments were 2.3 times
greater than that from HP ointment.
Case 2
A female patient (patient 2, age 77 years, 39 kg
body weight) with burns of 60 per cent TBSA
(50 per cent partial-thickness, 10 per cent mll-
thickness) was treated with 1200 g of each of
O-2 per cent tobramycin-CR, -PG and -HP
ointments during a period of 3 days from the
post bum days 3 to 5. The tobramycin peak
level after the application of tobramycin-CR
ointment was 6.6 ug/ml at 2.0 hour; the rate
of release of tobramycin from tobramycin-
PG ointment was a little slower than that of
tobramycin-CR ointment. However, that from
tobramycin-HP ointment was less than half of
those from tobramycin-CR and -PG ointments
(Fig. 2). The AUC values of cream and PG oint-
ments were also similar and 3 times greater than
that of HP ointment (Table I).
Case 3
The systemic absorption of a topically applied
tobramycin was also studied on a male patient
(patient 3, age 45 years, 60 kg body weight) with
full-thickness bums of 70 per cent TBSA. The
applied dose of O-2 per cent tobramycin-CR,
-PG or -HP ointment was 1400 g. Each of the
ointments was applied on the wound of the
patient during a period of 3 days from post burn
day 3 to 5. As shown in Fig. 3, the peak level
of serum tobramycin after the application of
tobramycin-CR ointment base was 5.1 ugrnl at
 E
Tab/e //. Burned patients examined 0
c
Area applied (% of TBSA) Tobramycin-PG Tobram ycin Postburn day 3
m
Case Age Sex Body weight (kg) Total PB FB BU ointment applied (g) absorption (AM) tested 3
P
I
w
25 M 61 90 90 1800 0.09 7
s
42 F 50 35 35 700 0.08 7 0.
30 M 49 70 55 15 1400 0.05 7 0”
o-
Partial thickness burn 22 M 54 50 50 1000 0.05 7 ‘;
7 3
70 F 50 70 70 1400 0.04
55 M 8 5.
54 80 80 1600 0.03 3
39 M 60 30 30 600 0.06 7
mean 0.06
1 28 M 60 60 60 1200 0.04 8
2 41 M 60 75 20 55 1500 0.02 7
3 33 M 60 30 30 600 0.05 5
4 16 M 50 30 30 600 0.02 9
Full thickness burn 5 38 F 55 11
50 5 45 1000 0.02
6 49 M 33 40 10 30 800 0.04 7
7 49 M 60 40 10 30 800 0.04 9
\B 76 F 42 30 30 600 0.01 3
9 72 F 52 50 50 1000 0.004 5
mean 0.03
1 53 M 20 20 400 0.31 122
2 53 M :z 25 25 500 0.16 32
Burn ulcer 3 33 M 53 20 20 400 0.19 38
4 64 F 43 20 20 400 0.1 1 38
5 64 F 35 30 30 600 0.08 76
6 46 M 42 24 24 400 0.07 27
mean 0.15

PB, partial thickness burn; FE, full thickness burn; BU, burn ulcer; AUC, area under the curve of tobramycin blood level (ug.hour/ml.g); PG.
polyethylene glycol.
296 Burns Vol. lo/No. 4

16

510
z
.g 6
::
56

-0 1 2 3 4 5 6 7 6 9 10 11 12
time after application (hrs)

Fig. 6. Systemic absorption of topical tobramycin in partial-thickness bums.

310
E
b
z 6.

-0 1 2 3 4 5 6 7 6 9 10 11 12
time after application (hrs)

Fig. 7. Systemic absorption of topical tobramycin in full-thickness bums.

2.0 hours and the level was maintained until 8 Case 4

hours. The rate of release oftobramycin after the A male patient (patient 4, age 74 years, 65 kg
application of tobramycin-PG ointment is simi- body weight) with bum ulcer of 20 per cent
lar to that of tobramycin-cream ointment, but TBSA, was treated during a period of 3 days
higher than that of tobramycin-HP ointment. from the postbum days 30 to 32. The applied
The tobramycin level after the applicaton of dose of each of 0.2 per cent tobramycin-CR -PG
tobramycin-HP ointment was not elevated. The or -HP ointment was 400 g. As shown in Fig. 4,
value of AUC of the cream was 1.4 and 2.3 times the peak levels of serum tobramycin after the
larger than those of the PG and HP ointments applications of tobramycin-CR, tobramycin-PG
respectively (Table I). and tobramycin-HP ointments were 6.3 f&ml at
Aoyama et al.: Ointment bases and tobramycin 297

0
0 1 2 3 4 5 6 7 6 9 10 11 12
time after application (hrs)
Fi,q 8. Systemic absorption of topical tobramycin in burn ulcers.

age 76 years, 39 kg body weight) with bum ulcer

. of 30 per cent TBSA during a period of 3 days
from postbum days 25 to 27. The dose of 0.2
per cent tobramycin-CR, -PG or -HP ointment
was 600 g. Fig. 5 shows that the peak level
of serum tobramycin after the application of
tobramycin-PG ointment was 6.0 ug/ml at
3.0 hours which is higher than that of
. tobramycin-CR ointment (5.0 kg/ml at 2.0
hours) and the rate of release of tobramycin from
. tobramycin-HP ointment was very low (I .O
0

ug/ml at 2.0 hours). The value of AUC of the

.
cream was slightly less than that of the PG oint-
ment, but 4.5 times higher than that of the HP
.
. . ointment.

.1
. -

. .= Application of tobramycin-PG ointment to

... .
. 4
... various degrees of burn
Among the ointment bases tested, it has been
full thickness p&iii thickness demonstrated that the cream or PG ointment are
burn ulcer
burn wound better than the HP ointment for systemic
absorption of tobramycin. For the treatment of
Fig. 9. Systemic absorption of topical tobramycin in various degrees of bum, tobramycin-PG oint-
partial-thickness bums, full-thickness bums and bum ment was chosen and tested as shown in Table
uicers. II. Serum concentrations of tobramycin after the
applications of tobramycin-PG ointment to 7
patients with partial-thickness bum, 9 patients
2.0 hours, 5.9 pg/ml at 4.0 hours and 4.2 &ml with full-thickness burn and 6 patients with
at 1 hour. The value of AUC of the cream was burn ulcer areshown in Figs. 6-8.
1.2 times and 1.5 times larger than those of PG In partial-thickness bums the serum con-
and HP ointments, respectively (Table I). centration of tobramycin rose quickly with a
peak level 3-4 hours after the application of
Case 5 tobramycin-PG ointment. The highest serum
The absorption of topically applied tobramycin level of tobramycin, 16.3 &ml, was obtained in
was also studied in a female patient (patient 5, the patient with partial-thickness bum (90 per
298
cent TBSA) 3 hours aher the application. The
serum concentration of tobramycin decreased
gradually, horn 5 hours after the application.
In full-thickness bums, the serum level did
not greatly increase after the application of
tobramycin-PG ointment, and the peak level
was below 5 l&ml.
In bum ulcers, the serum level of tobramycin
after the application of tobramycin-PG oint-
ment increased quickly with the peak level
in serum l-2 hours after the application.
Three hours after the application, it decreased
gradually. Thus the penetration of tobramycin
through wounds to the blood circulation in burn
ulcers was faster than that in partial-thickness or
full-thickness bum wounds.
As shown in Table II and Fig. 9, the mean
values of tentative AUC of tobramycin-PG oint-
ment in partial-thickness and full-thickness
bum wounds were 0.06 and 0.03, while that in
bum ulcers was 0.15. Thus the absorption of
tobramycin in patients with partial-thickness
bum wound was about twice as great as that in
patients with full-thickness bum, and in patients
with bum ulcer it was about 5 times greater than
in patients with full-thickness bum.
DISCUSSION
It is generally recognized that an ointment
vehicle (base) may affect drug penetration into
the blood by modifying the penetration of
burned skin and the release of the drug from the
vehicle. From in vitro studies using burned ani-
mals, Harrison et al. (1972) estimated the tissue
accumulation of sulphamylon acetate from topi-
cal applications of a 5 per cent aqueous solution
and a 5 per cent cream into excised burned tissue
of the rat. The absorption of sulphamylon acet-
ate from aqueous solution was greater than that
from cream base. Robb et al. (198 1) reported the
absorption of silver sulphadiazine in rats from a
solid dressing formed by mixtures of PG 400 and
poly-2-hydroxyethyl methacrylate and from
cream, and found that the level of silver in the
blood following treatment of the burned wound
with topical silver sulphadiazine was signifi-
cantly less when the drug was presented in the
solid dressing than when the drug was applied in
a cream base. In burned patients, by determining
the gentamycin concentration in urine. Stone et
al. (1968) demonstrated greater absorption of
gentamycin from cream (a mixture of various
organic acids with oil to make the solution
water miscible) than from petrolatum (brand
petrolatum).
ln our results, the systemic absorption of
Burns Vol. lo/No. 4
tobramycin into blood was also greater from the
oil-in-water base, CR or PG ointments than
from the water-in-oil base, HP ointment in
burned wounds and burn ulcers of the patients.
In intact skin, it has been reported that the
absorption of topical agent was greater in HP or
petrolatum than in PG ointment (Ghanem et al.,
1978). However, the absorption of a drug is
greatly reduced by the epidermis skin barrier in
normal skin (Fitzpatrick 1979). Intact skin has
an epidermis which functions as a barrier against
topical agents, but it is well-known that a topical
drug mixed with a water-in-oil or oil base can
easily penetrate through this epidermis.
In contrast, the bum wound loses epidermis
(skin barrier) and has a larger water content,
such as occurs in the immediate postbum period
with local oedema and during later stages when
there is a profuse exudation from bum wounds
or bum ulcers. So, in bum wounds, topical
agents in a water miscible base are easily
absorbed. For example, silver sulphadiazine was
found to be easily absorbed in partial-thickness
burned areas of the rat after removal of blister
skin (Sano et al., 1982) and sulphamylon was
readily absorbed in human partial-thickness
bums (White et al., 1971; Pruitt et al., 1973).
Our data with tobramycin also demonstrate a
high absorption of topically applied drug in an
area of partial-thickness bum.
In full-thickness bum, the mass of avascular
and non-viable tissue (eschar) is present on the
surface of the burn wound, and might reduce the
absorption of the topically applied drug.
In an in vivo study, however, it was demon-
strated that gentamycin, sulphamylon, nitro-
furazone, povidone-iodine, silver nitrate and
silver sulphadiazine could penetrate the eschar
and retain their effectiveness after penetration
(Stefanides et al., 1976). Harrison (1969, 1979)
also reported the moderate absorption of sul-
phamylon and silver sulphadiazine in full-thick-
ness bum, but Sano (1982) found that silver
sulphadiazine could not easily penetrate the
full-thickness burned area. The other clinical
data demonstrated the small absorption of top-
ically applied agents (silver sulphadiazine, gen-
tamycin, sulphamylon) through full-thickness
bum wound (Fox et al., 1969; Stone, 1971;
Pruitt et al., 1973). In some cases, a high absorp-
tion of iodine was reported after topical appli-
cation of povidone-iodine (Lavelle et al., 1975;
Pietsch et al., 1976; Hunt et al., 1980). These
results suggest that the absorption of topical
agents through full-thickness bum wound
remains incompletely understood.
Aoyama et al.: Ointment bases and tobramycin
The present data indicated that tobramycin is
absorbed through full-thickness burn areas, but
less readily than through partial-thickness burn
areas. In burn ulcers, there is no epidermis or
eschar, so the absorption of a topically applied
drug might be great. Our results clarify the rapid
absorption of water soluble antibiotics, such as
tobramycin, through partial-thickness burn
areas and burn ulcers.
As shown in Figs. l-5, serum levels of tobra-
mycin reached 5.0-6.6 pgg/ml and this level con-
tinued for several hours when the tobramycin
ointments (oil-in-water bases) were applied on
the burn wound surface.
This level of tobramycin is thought to be at
the therapeutic level (S-10 pg/ml) (The Pharma-
ceutical Codex, 1979). With regard to the
toxicity of tobramycin, it has been reported that
a peak concentration of tobramycin in excess of
IO-12 Fg/ml has been associated with ototoxi-
city and, to some degree, nephrotoxicity.
These data, including the present ones, suggest
that additional administration of tobramycin per
OS or by injection should be made carefully to
avoid the toxicity of tobramycin when patients
with partial-thickness bums and burn ulcers are
treated with tobramycin ointments, especially
when cream base or PG base is used as a vehicle.
REFERENCES
Brogden R. N., Pinder R. M. and Sawyer P. R. (1976)
Tobramycin: a review of its antibacterial and
pharmacokinetic properties and therapeutic use.
Drugs 12, 166.
Fitzpatrick T. B., Eisen A. Z., Wolf K. et al. (1979)
Dermatology in General Medicine. USA, Macgraw-
Hill
Fox C. L., Rappole B. and Stanford W. (1969) Silver
sulphadiazine-an organic complex for topical
chemotherapy of pseudomonas infections in bums.
In: Pharmacological Treatment in Burns. Amster-
dam, Excepta Medica, p.224.
Ghanem A. H., El-Sabbagh H. M. and El-Helw A. M.
(1,978) Effect of liauid additives on release of chlor-
gmphknicol from’ointment bases. Pharmazie 33,
443.
Harrison H. N., Blackmore W. P., Dressler D. P. et al.
(1969) Absorption and metabolism of 14C labeled
sulfamylon acetate. In: Pharmacological Treatment
in Burns. Amsterdam, Excepta Medica, p.204.
Correspondence should he addressed lo: Hisashi Aoyama
Nagoya 457, Japan.
Harrison H. N., Bales H. W. and Jacoby F. (1972) The
absorption into burned skin of sulfamylon acetate
from 5 per cent aqueous solution. J. Trauma 12,
994.
Harrison H. N. (1979) Pharmacology of sulfadiazine
silver. Arch. Surg. 114,28 1.
Hunt J. L., Sato R., Heck E. L. et al. (1980) A criti-
cal evaluation of povidone-iodine absorption in
thermally injured patients. J. Trauma 20, 127.
Lavelle K. J., Doedens D. J., Kleit S. A. et al. (1975)
Iodine absorption in bum patients treated with
povidone-iodine. Clin. Pharmacol. Ther. 17, 355.
Pietsh J. and Meakins J. L. (1976) Complications of
povidone-iodine absorption in topically treated
bum patients. Lancet 1, 280.
Pruitt B. A., Mason A. D., Foley F. D. et al. (1973)
Use of sulfamylon in burned patients. In: Lynch J.
B. and Lewis S. R. Svmoosium on the Treatment of
Burns, Saint Louis, Moiby, p. 117.
Robb E. C. and Nathan P. (198 1) Control of exper-
imental bum wound infections: comparative deli-
very ofthe antimicrobial agent (silver sulphadiazine)
either from a cream base or from a solid synthetic
dressing. J. Trauma. 21. 889.
Sano S.,-Fujimori R., Tgkashima M. et al. (1982)
Absorption excretion and tissue distribution of
silver sulnhadiazine. Burns 8. 278.
Shelmire J.* B. (1960) Factors ‘determining the skin-
drug-vehicle relationship. Arch. Dermat.-82, 78.
Stefanides M. M.. Coneland C. E.. Kominos S. D. et
.
al. (1976) In vitro penetration of topical antiseptics
through eschar of bum patients. Ann. Surg. 183,
358.
Stolar M. E., Rossi G. V. and Barr M. (1960a) The
effect of various ointment bases on the percutaneous
absorption of salicylate I. J. Am. Pharm. Assoc. 49,
144.
Stolar M. E., Rossi G. V. and Barr M. (1960b) The
effect of various ointment bases on the percutaneous
absorption of salicylates II. J. Am. Pharm. Assoc.
49, 148.
Stone H. H., Kolb L. D., Pettit J. et al. (1968) The
systemic absorption of an antibiotic from the burn
wound surface. Am. Surg. 34, 639.
Stone H. H. (1971) Wound care with topical gen-
tamycin. In: Polk H. C. and Stone H. H. (ed.)
Contemporary Burn Management. Boston, Little
Brown, p.203.
White M. M. G. and Asch M. M. J. (1971) Acid-base
effects of topical mafenide acetate in tie burned
patient. N. Engl. J. Med. 284, 1281.
The Pharmaceutical Codex, 1lth edition (1979)
London, The Pharmaceutical Press, 1949.
Paper accepted 4 August 1983
MD, Department of Bums and Plastic Surgery, Chukyo Hospital,