oral administration of phenoxymethyl penicillin

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ORAL ADMINISTRATION OFPHENOXYMETHYL PENICILLIN

(DISTAQUAINE V)By L. HENRY, M.B., Ch.B., M.R.C.S., L.R.C.P.

Senior House Officerand M. J. MEYNELL, M.D., M.R.C.P., D.P.H.

Clinical PathologistFrom the Department of Clinical Pathology, The General Hospital, Birmingham

The oral administration of penicillin has manyadvantages, and a number of reports have beenpublished on various preparations. In all of theseabsorption was found to be very irregular, largedosage being required to maintain satisfactoryblood levels. (Wright et al., 1953 ; Fairbrother andDaber, I954; Cathie and MacFarlane, 1953; Doxi-adis et al,. 1951.) In order to provide more reliableabsorption, Phenoxymethyl Penicillin ('Dista-quaine V') has recently been introduced in thiscountry. Although it has been in use on theContinent (Brandl et al., 1953), no reports have yetappeared in the English literature. This papergives the results of a limited survey of serumpenicillin levels after the oral administration of'Distaquaine V' to three patients and 12 normalsubjects whose ages ranged from i8 - 47 years.MethodThe tablets contain 60 mg. 'Distaquaine V'

(approx. Ioo,ooo units) and each subject had bloodestimations performed after the ingestion of I, 2and 4 tablets. The dose was given well before themid-day meal and blood was withdrawn at hourlyintervals, the serum being separated as soon aspossible and the titration carried out on the sameday. The serum penicillin levels were estimatedby a serial dilution method using Glucose Andradepeptone water inoculated with one drop of anovernight broth culture of the Oxford strain ofStaphylococcus aureus (sensitive to 0.02 units ofpenicillin per c.c.). Readings were taken afterincubation for i8 hours at 37°C. and the end pointwas based on colour change and visible growth,both being compared with a control of normalserum containing a known amount of penicillin.

In some instances it was found necessary to sub-culture on to a solid medium to ascertain theend-point.ResultsThe serum penicillin levels obtained are shown

in Tables i-3 and Figs. I-3. Fig. 4 is a graphof the average levels for all three doses.

SUBJECT HOURS

I 2 3 4

G.W. .16 . . 08 .04A.L. .8 o8.8.o8 04M.J.M. .o8 .o8 .04 .04L.H. . 6 .o8 .04 .04M.A.B. .32 .o8 .04 .04A.C.A. .16 .o8 .04 .04E.T. .64 .04A.R.T. . 6 .o8 .04A.E.J. .32 .o8 .04P.J.D. I.28 .16 .04A.T. . 6 .o8 .o8 .o8N.C.B. .04 .o8 .16 .i6

AVERAGELEVELS .3 .o8 .o6 .04

TABLE I. Serum Penicillin levels (units/c.c.) in I2normal subjects after administration of1oo,ooo units of Distaquaine V.

SUBJECT HOURS

I 2 3 4 5 6

G.W. .64 .i6 .04 .04 .04 -A.L. .32 . 6 .08 8 .o 8.804M.J.M. .64 .32 .08 .04 -

L.H. .64 . 6 .08 .04M.A.B. .64 .32 .08 .04A.C.A. .64 .32 .08 .04E.T. 2.56 .I6 .04 -

A.R.T. .64 .16 .08 - -

A.E.J. .16 .64 .32 .16P.J.D. 1.28 .32 .08 - -

A.T. . 6 .32 .i6 .08N.C.B. .64 .64 .i6 .08 -

AVERAGELEVELS .75 .3 .I .05 .01 -

TABLE 2. Serum Penicillin levels (units/c.c.) in I2normal subjects after administration of200oo,ooo units of Distaquaine V,

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298 POSTGRADUATE MEDICAL JOURNAL Jtune 1956

SUBJECT HOURS

I 2 3 4 5 6

G.W. 1.28 1.28 1.28 .32 .0o8 .04A.L. 2.56 .64 .32 o8 .04 -M.J.M. 1.28 i.28 .32 .08 -L.H. 1.28 .32 .i6 .8 -

M.A.B. 2.56 .64 .32 .o8 -

A.C.A. 2.56 1.28 .32 .6 - -E.T. 5.I2 .64 .i6 .04A.R.T. 2.56 .32 .32 .o8 .4 -A.E.J. - 2.56 1.28 .64 .6 .o8P.J.D. 5.12 i.28 .i6 .04 -

A.T. .64 I.28 .64 .i6 .o8 .04N.C.B. .32 i.28 .64 .64 .32 .i6

AVERAGELEVELS 2.I I.0 .49 .2 .06 .025

TABLE 3. Serum Penicillin levels (units/c.c.) in 12normal subjects after administration of400,000 units of Distaquaine V.

These levels are uniformly higher than thoseobtained with other preparations of penicillin, buteven so, extreme individual variation was stillencountered. This can be seen from Table 3where, one hour after a dose of 4 tablets, levelsranged from nil to 5.I2 units per c.c. Individualvariation was also noted, and in the case of one

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June 1956 HENRY: Oral Administration of Phenoxymethyl Penicillin (Distaquaine V) 299

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subject (A.E.J.), the peak level was progressivelydelayed, the i-hour levels decreasing as the dose'was increased. However, in view of the levelsobtained and their duration, it was felt that thepreparation was satisfactory for clinical use. Inorder to demonstrate any cumulative effect, dailyestimations were performed on three patientsreceiving 2 tablets 6-hourly. Each day for threedays blood was taken immediately before the mid-day dose and again at I.o p.m. The results areshown in Table 4 and probably represent indivi-dual variation rather than a cumulative effect.

Ist Day. 2nd Day. 3rd Day.PATIENT 12.0 I.O. 12.0 I.0 12.0 I.0

noon p.m. noon p.m. noon p.m.x. .08 .64 Nil .32 Nil .642. .o8 .32 .04 1.28 .04 i.283. Nil .64 Nil 0.64 Nil 1.28

TAbLE 4. Serum Penicillin levels (units/c.c.) in patientsreceiving 200,000 units Distaquaine V 6hourly. Estimations performed before themidday dose and i hour later.



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300 POSTGRADUATE MEDICAL JOURNAL June 1956

Side EffectsThree of the normal subjects experienced mild

abdominal discomfort and borborygmi, but therewas no nausea, vomiting or diarrhoea.

SummarySerum penicillin levels were estimated on I2

normal subjects using varying dosage of 'Dista-quaine V'.The levels obtained and their duration were

considered satisfactory, although considerable in-dividual variation was still encountered.

In three patients receiving treatment with'Distaquaine V' no cumulative effect was noted.

We wish to thank Miss M. A. Butcher fortechnical assistance, Miss M. N. Ellis for typingthis report, and the twelve 'volunteers' from theLaboratory.

This work was carried out with the help of agrant from the Endowment Research Fund of theUnited Birmingham Hospitals.

BIBLIOGRAPHYBRANDL, E. et al. (1953), Wien. Med. Wchnschr., 103, 6oz-7.CATHIE, I. A. B. and MacFARLANE, J. C. W. (1953), B.M.J.,

ii, 805.DOXIADIS, S. A. et al. (I9S5), B.M.J., i, x6.FAIRBROTHER, R. W. and DABER, K. S. (1954), Lancet, i, 17,

858.WRIGHT, S. S. et al. (1953), Journal of Laboratory and Clinical

Medicine, 42, 3, 417.

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