Influence of the cupric ion on the ampicillin concentration in cervical mucus

CONTRACEPTION

INFLUENCE OF THE CUPRIC ION ON THE AMPICILLIN CONCENTRATION IN CERVICAL MUCUS

Jan Moesgaard, M.D. Christine

Felding,

M.D.

Svend Steenstrup-Pedersen, Alice Friis-MrWer,

M.D. M.D.

Department

of Gynaecology

Department

of Microbiology

Bispebjerg Copenhagen,

Hospital Denmark

ABSTRACT The copper ion is known to inactivate fall in ampicillin copper-IUD,

was investigated.

concentration. of ampicillin

Submitted Accepted

concentration Furthermore,

for publication

molecule -in vitro. The possible mucus, before and after insertion of a

There was no significant no correlation

in serum and cervical

for publication

the penicillin

in cervical

change in the ampicillin

was found between

the concentrations

mucus.

April 7,1982 April 14, 1982

MAY 1982 VOL. 25 NO. 5

471

CONTRACEPTION

INTRODUCTION It has long been known that metal Several

authors

catalyze

that

hydrolysis

of penicillins

well

that

It is also contraception

known

after

insertion after

using

higher phase

of

the

removal

mildly

penicilloic

acid (1, 2, 4, 5).

IUD,

the

Copper-T

and

there

device

of copper

The increase

of the IUD.

antibiotics

the cupric

concentration

(3).

on various

acid conditions

to the non-active

women

in the proliferative

concentration

ions have an influence under

have significantly

especially gained

have shown

for

intrauterine

in cervical

in concentration

is a rapid

fall

The serum concentration

(6).

ion will

mucus,

is quickly

of

the

copper

of copper

is not

altered. It might genital

be expected tract

reduced.

that

infection

This hypothesis

correlation

between

the effect

in women

of antibiotics

used in the treatment

using a copper-IUD

is the reason

the concentrations

for contraception

for the present of ampicillin

study.

in serum

of lower would be

Furthermore, and cervical

the mucus

is sought.

MATERIAL AND METHODS Ten fertile who visited wanted

healthy the

women, outpatient

with no recent department

an IUD for contraceptive

penicillin-allergy All patients

were

reasons.

received

the proliferative

infection, All women

with known or suspected

mucus samples

of the IUD, the patients

orally

and samples

of the ampicillin new measurements

were studied

were taken before

Before

insertion

The IUDs were inserted

were

insertion

in

with the IUD in situ

the same day as the insertions

each woman serving

472

tract

to participate.

the same type of IUD; Cu-T-200.

one month later,

one month,

asked

No patients

phase (6-l 1 day), and the patients

Blood and cervical

determination

of lower genital

were asked.

in the next cycle on approximately

Probenicid

history

were made.

of the IUD and again

as her own control. received

taken

350 mg Pivampicillin

approximately

concentration were performed

in serum

and 500 mg

one hour afterwards and cervical

mucus.

for After

with the IUD in situ.

MAY 1982 VOL. 25 NO. 5

CONTRACEPTION

The ampicillin Bispebjerg

concentrations

Hospital,

To determine culture

the

Copenhagen, ampicillin

18 h on trypticase

absorbed

on sterile

solutions

of ampicillin

were

analysed

concentration

discs

Signed

Rank

and placed

possible

fall

insertion

of the IUD.

before

and after

mucus,

were

on the agar plates.

Cervical immersed

The plates

lutea

mucus was in standard

were incubated

at

zones were determined. as statistical

concentration

the correlation

a sarcina

afterwards

was used

in ampicillin

To investigate ampicillin

Statistic

in cervical

was used as medium.

which

37’C for ‘24 hours and the inhibition Pratt

of Microbiology,

Denmark.

agar plates

filter

by the Department

between

insertion

method

in cervical

mucus

serum and cervical

of IUD, Spearman’s

to determine before

the

and

after

mucus concentration

of

test was used.

RESULTS Table I shows the concentrations and after

insertion

concentration

There

of Cu-T-200.

in cervical

The ampicillin

of ampicillin

mucus after

concentration

insertion

in cervical

in serum and cervical

is no significant

mucus before

falI in the ampicillin

of a coppelr_IUD (p >O.OS).

mucus/ampicillin

concentration

in serum

ratio is shown in Table II. The correlation

coefficient

mucus before

insertion

these

is significant.

Before

figures

insertion

for the ampicillin

of IUD is 0.13 and after

concentration insertion

of the IUD, the mean ampicillin

was 16.2% (5-40%) of the serum ampicillin

in serum and cervical

of the IUD 0.503.

concentration

concentration

in cervical

None of

mucus

and after

insertion

of the

during the first

IUD 15.2% (5-40%).

DISCUSSION It is known that

the release

of copper

from a Cu-T-200

is highest

therefore

be expected

if there

60 days of use (3).

It might

effect

ion on the ampicillin

of the cupric

MAY 1982VOL. 25 NO. 5

molecule

that

was a hydrolytic

as shown -in vitro (1, 2, 4, 5), the

473

CONTRACEPTION

TABLE1

miBix

II

Concentrations of ampicillin

Concentrations of a@-

in serum and cervicalmucus

cillin:cervical mucus/

before and after copper-IUD

serum.

Patient

La

semn-conc. cerv.muc.conc.

3.50

0.46

2,50

0.46

2.a

4.50

0,62

b

6.00

1.30

3.a

5.25

1,40

b

9.60

0.5

4.a

8.50

0.70

b

7.60

0.22

5.a

6.20

0.28

b

16.00

0,84

8.4

0.52

b

10.00

4.00

7.a

10.50

1.40

b

6.a

b

12.00

1.50

8.a

8.60

1.20

b

14.00

1.90

9.a b

5.60

1.50

8.60

0.90

.O.a

4.70

1.90

9.80

3.00

b

Before IUD After IUD

0.13

0.18

0.14

0.22

0.27

0.05

0.08

0.03

0.05

0.05

0.06

0.40

0.13

0.13

0,14

0.14

0.27

0.10

0.40

0,31

MAY

1982 VOL. 25 NO. 5

a=valuebeforeinsert.ionof IUD b=value after insertionof IUD

474

CONTRACEPTION

effect

would be most evident in the first two or three cycles after insertion

copperIUD.

Of a

In spite of this, we have not been able to prove our hypothesis,

though the copper concentration

in cervical

even

mucus was higher than the concen-

tration of copper _in vitro during physiological conditions. There was no significant

fall of the ampicillin

concentration

before and approximately

30 days after insertion

of a copper IUD.

there were no changes in the serum concentration be expected constitutes

as the amount

of ampicillin.

mucus

Furthermore,

This could hardly

from the IUD per 24 hours only

l-2% of the daily copper intake (3).

There was no correlation ampicillin

of copper released

in cervical

neither

between

the serum and cervical

before nor after

uptake of ampicillin

in cervical

insertion

mucus.

mucus concentration

of the IUD.

of

This suggests different

The reason for this is not a matter of this

study. CONCLUSION Insertion

of a copper IUD does not cause a fall of the ampicillin

cervical

mucus.

treatment

Therefore,

concentration

there is no reason to remove a copper-IUD

of a lower genital tract infection

no reason to increase the dose of ampicillin

with ampicillin.

Furthermore,

in

before there is

given to women using the coppepIUD.

REFERENCES 1.

Cressman, penicilloic

2.

Cressman, penicillins:

W.A., Sugita

E.T. et al.:

acids by cupric ion. J>harm.

Complexation Pharmac.

of penicillins

and

18:801-808 (1966).

W.A., Sugita E.T. -et al.: Cupric ion-catalyzed’ hydrolysis of Mechanism and site of complexation. J. Pharm. Sci. Vol.

58.x:1471-1476 (1969). 3.

Hagenfeldt, Contraception

K.:

Intrauterine

contraception

with

the copper-T-device.

vol. 6,1:3’7-54 (1972).

MAY 1982 VOL. 25 NO. 5

475

CONTRACEPTION

4.

P.J. -et al.: Efect of copper (II) - glycine chelates of penicillin in mildly acid solution. J. Pharm. Sci. Vol. ‘61,

Harwood, R.J., Niebergall, on degradation 1:82-86 0972).

5.

6.

Niebergall,

P.J., Hussar,

antibiotics.

J. Pharm. Pharmac.

Ujiie,

Influence

H.:

Nippon Saikingaku

476

D.A. -et al.: Metal binding l&729-738 (1966).

of metal

Zasshi

ions on the action

x:771-775

tendencies

of several

of various

antibiotics.

(1955).

MAY 1982 VOL. 25 NO. 5