ANNALS O F C L IN IC A L A N D LABO RA T O RY S C IE N C E , Vol. 6, No.

3
Copyright © 1976, Institute for C linical Science

Drug Interference in Laboratory Testing

D O N A LD T. FORM AN, Ph.D .*
and D O N A LD S. YOUNG, M.B., P h.D .f
*D epartm ent o f Pathology i? Laboratory M edicine,
E vanston H ospital,
E vanston, IL 60201
and
\Clinical Center,
National Institutes o f Health,
Bethesda, MD 20014

ABSTRACT
C haracteristic problem s in th e interpretation of laboratory data w h en a
drug or its m etabolite interferes w ith a laboratory procedure are review ed.
Various m echanism s of interference (physical, chem ical, pharm acological
and drug-drug interaction) are discussed. T he role o f a com puterized drug-
test interference file in assisting in th e prediction as w ell as interpretation
of apparent test results is described.

Introduction tic le on th e ch em ical an d d iag n o stic

O ver th e past decades, the practice of specificity of laboratory tests. In 1964,
m ed icin e has u n d erg o n e con sid erab le B orushek and G old 1 published an article
sophistication. P otent new drugs in prac­ containing a list of drugs interfering w ith
tically every therapeutic category are avail­ routine endocrine procedures. W irth and
able. W henever a patient receives a T hom pson ,19 in 1965, pu blished a list o f
drug, there is a possibility of drug-test in ­ substances and conditions w hich affect
terferences. W hen m ore than one drug is th e re su lts o f lab o rato ry p ro c e d u re s.
adm inistered, th ere m ay also be drug- T hey included such factors as tem pera­
drug interactions. T hese developm ents ture, light and drugs. O ther review arti-
h av e c re a te d n ew p ro b le m s for th e cles 8,11,14,17 have b een of great value in
laboratory scientist. A characteristic prob­ helping to define this problem .
lem is th e in terp retatio n o f laboratory O ne of the m ost am bitious approaches
data w hen a drug or its m etabolite may to this problem has b een the develop­
in terfere w ith a laboratory proced ure. m ent of a 9000-entry com puter-file based
O ne drug m ay affect the action o f another on a compilation of 1030 literature refer­
given at the same tim e, thus changing the ences .20 This com puterized com plication
value of a test result. of effects of drugs on laboratory tests has
N um erous attem pts have b een m ade b een used to assist in th e interpretation
by a num ber of com pilations and articles o f u n u su al te st resu lts in th e clinical
to d o c u m e n t th e s e effe c ts. In 1962, chem istry laboratories of th e N ational In ­
Caraw ay 2 pu blished a com prehensive ar­ stitutes of H ealth and the E vanston Hos-
263
264 FORMAN AND YOUNG

TABLE I
M echanism s of Interference
Colored Urines Due to Drugs or Metabolic Disorders T here are four distinct m echanism s of
interference in laboratory testing. Physi­
Color o f Urine Cause Disorder
cal, c h e m ic a l, p h a rm a c o lo g ic a l an d
drug-drug interactions are of special in­
Orange-red Phenazopyridine
Phenindione
Drug related
te re st to th e lab orato ry scien tist. T he
Phensuximide m echanism s of th e interferences w ill be
briefly review ed and, w herever possible,
Red Porphyrins Congenital
porphyria
Acute
intermittant
solutions suggested.
Red-brown Hemoglobin and
porphyria
Crush
P h y s ic a l E f f e c t s
derivatives syndrome D rugs may interfere w ith colorim etric
Urobilin Hemolytic
anemia photom etric or fluorom etric analyses by
Yellow
Green-yellow
Chloroquine Drug related
im parting a characteristic color to the
specim en. In table I are described som e
Bile pigments Regurgitative
jaundice
Blue Methylene blue
Triamterene
Drug related
unusually colored urines and their rela­
Blue Indigo compounds Intestinal tio n sh ip to d ru g a d m in istra tio n or
m etabolic disorders. T his type of inter­
disease
(indicanemia)
Blue-green Aiaitripty 1ene Drug related
fe re n c e can b e d e te c te d v isu a lly by
laboratory person nel and drug interfer­
Brown-black Melanin Malignant
melanoma
Homogentisic Acid Alkaptonuria
ences may be circum vented by collecting
th e specim en after an appropriate length
of tim e during w hich th e drug in question
pital of N orthw estern U niversity M edical has b een discontinued. T here are m any
C enter, as w ell as in som e other centers. v arieties o f drugs an d foods th a t can
A major problem facing users of the cause th is ty p e of in terference. T h ese
various collations of laboratory test inter­ should be co n sid ered first as possible
ferences is the relationship betw een drug causes of any unusually colored urine.
dosage and diagnostic test interference Som e drug s act as in d icato rs (e.g.,
and the possible synergistic effect of sev­ p h e n o lp h th a le in , v eg etab le laxatives)
eral drugs. T he m etabolic and clinical and affect tests carried out at a particular
states of the patien t also affect the degree pH . T he p resence of sulfobrom ophtha-
of laboratory in terferen ce. If an in d i­ lein dye (BSP) in serum w ill interfere
vidual has norm al kidney and liver func­ w ith serum protein determ in ed by the
tion, the response w ill be different to a b iu ret m ethod. T h e dye is colorless at the
drug dosage than that of th e patien t w ho pH of blood b u t pu rp le w hen m ade al­
is unable to detoxify or to excrete the kaline during th e assay.
com pound. C h e m ic a l E f f e c t s
D rugs m ay b e m easured as analytes,
In order to cope w ith the problem of e ith e r b e c a u se o f th e ir sim ila rity in
drug induced m odifications of laboratory chem ical structure or because they con­
test values, laboratory scientists should tain a com ponent th at is an analyte. P a­
possess an understanding of th e m ech­ tients w ho have receiv ed radiographic
anism s involved in these interferences. con trast m ed ia co n tain in g io dine w ill
T he purpose of this article is to consider have an altered protein-bound iodine, al­
these m echanism s and to discuss the role though thyroxine is not affected w hen d e­
of the com puterized drug-test interference term in ed by protein bin d in g m ethods.
file in the prediction as w ell as the inter­ T he m ost serious and long-lasting inter­
pretation of apparent test results. ferences are those caused by intraven­
 DRUG INTERFERENCE IN LABORATORY TESTING
ously adm inistered iodinated radiopaque
agents (e.g., acetrizoate and adipiodone).
T he drugs orabilex and dionsil have a
negligible effect on th e analysis of pro­
tein b o un d iodine at a concentration no
greater than 100 fig p er dl, b u t seriously
affect the procedure at 1000 fig per dl.
Serum potassium concentration is in ­
creased by the concurrent adm inistration
of intravenous potassium penicillin G.
T he penicillin preparation contains 1.7
m m ol o f potassium per m illion units.
Thus, a patien t receiving 10 m illion units
of th e antibiotic receives 17 m m ol (m Eq)
o f potassium .
A chem ical interference m ay also result
w hen the substance b eing determ ined
reacts in vivo w ith a drug adm inistered
prior to th e collection of blood for
analysis. F or exam ple, serum calcium de­
term inations m ay be affected by the ad­
m in istratio n of th e ch elatin g agent,
ethylenediam inetetracetate (ED TA ).3 In
certain conditions such as lead poisoning
and collagen disease, E D T A has b een
used therapeutically to reduce th e lead
and calcium concentrations, respectively.
Less w ell recognized is th e fact th at vari­
ous chelating agents are also used as p re­
servatives to p reven t oxidation reactions
in drug preparations. In patients on
ED TA therapy, calcium cannot be de­
term ined by the indirect colorim etric or
fluorom etric m ethods based on th e chela­
tion o f a calcium —E D T A com plex. H ow ­
ever, in calcium d eterm in atio n s by
ato m ic-ab so rp tio n sp ectro sco p y , th e
com plexing agent is destroyed in the
flam e and th e direct concentration of cal­
cium can be determ ined.
D rugs can also interfere w ith labora­
tory results by negating certain non­
specific oxidation and reductions essen­
tial for the chem ical assay. Penicillin,
strep to m y cin an d ascorbic acid are
know n to react w ith cupric ion; thus, false
positive results for glucose may occur if a
copper reduction m ethod is used. If the
265
sp e c ific e n z y m a tic g lu co se-o x id ase
m ethod is em ployed, ascorbic acid can
cause a false negative result by preven t­
ing the oxidation o f a specific chrom ogen
in the reaction.
Increased transam inase activity has
been observed w hen the diazocolorim et-
ric m ethod is used. U nusually increased
activity has b een reported in patients
w ith ketosis and also in patients receiv­
ing erythrom ycin 13 or p-am inosalicylic
acid .9 T hese test interferences can be ob­
viated by em ploying ultraviolet kinetic
procedures.
C olorim etric procedures u sed in steroid
assays are often subject to drug interfer­
e n ce . In th e d e te rm in a tio n o f 17-
ketosteroids by th e Z im m erm an reaction,
drugs w ith th e 17-keto basic structure,
such as ascorbic acid, m orphine and re-
serpine, w ill cause increased values. In
th e determ ination of 17, 21-dihydroxy-
steroids by the Porter-Silber reaction, the
dihydroxyacetone chain is th e reactive
unit. D rugs like m eprobam ate, chloral hy­
drate, chlorprom azine and potassium io­
dine w ill interfere w ith this reaction and
cause elevated values. In the colorim etric
determ ination of vanillylm andelic acid
(VMA) by a diazo reaction, drugs like
m ethocarbam ol and m ethyl dopa cause
falsely elevated results.
W hen specific drugs have b een dem ­
onstrated to interfere w ith chem ical
reactions, patients should be m aintained
free of these drugs for at least 72 hours
before collecting the specim en. O ther
an aly tical te c h n iq u e s, e.g ., co lu m n
chrom atography and radioim m unoassay
procedures, can also be subm itted for an
affected m ethod.
Pharm acological Effects
This type o f interference usually re­
sults from the pharm acological or toxic
activity of drugs b u t m ay also arise from
th erap eu tic q u an tities of drugs. An
exam ple is the increase in prothrom bin
266 FORMAN AND YOUNG

TABLE II
and diabetics m ay require m ore insulin
Drugs Capable of Increasing Blood Glucose or oral antidiabetic drugs. Patients w ith
latent diabetes occasionally develop an
Dextrothyroxine Phenothiazines abnorm al glucose tolerance curve. Salicy­
lates have also b een reported to reduce
Diazoxide Steroids
Diphenylhydantoin Adreno cort icos teroids
Diuretics
Nicotinic acid
Estrogens
hyperglycem ia in diabetics and produce
hypoglycem ia in norm al children. In ta­
Sympathomimetic amines

bles II and III are listed various drugs

TABLE III
Drugs Capable of Decreasing Blood Glucose
Alcohol
Asparaginase
Monoamine oxidase inhibitors
Propoxyphene
Caffeine Propranolol
Haloperidol Anabolic agents
tim e w hich results from th e adm inistra­
tion of a therapeutic am ount of sodium
w arfarin. H ow ever, unexpected interfer­
ences resulting from side effects or ad­
verse reactions may create problem s in
the interpretation of laboratory data. D is­
turbances in fluid and electrolyte balance
a n d h y p o p o ta sse m ia are com m on.
T hiazide diuretics and large doses of
glucocorticosteroids may severely reduce
th e concentration of plasm a potassium .
A cetazolam ide and ethoxazolam ide m ay
cause m etabolic acidosis, raised serum
uric acid and low ered urinary excretion
of uric acid. A rise in serum uric acid has
also b een reported follow ing the ad­
m inistration of levodopa .4 T he thiazides
can also have a hyperglycem ic activity
TABLE IV
Hormone Levels in Women on Oral Contraceptives*
Level in Level in Women
Menstruating on Oral
Women Contraceptives
capable of increasing or decreasing blood
glucose in non-diabetic subjects.
H ydantoin anticonvulsants m ay cause
th e appearance o f positive lupus erythem ­
atosus (L.E.) cells and m ethem oglobin­
em ia. C hlorprom azine has also been
im plicated in causing a syndrom e like
system ic lupus erythem atosus w ith ac-
com paning positive tests for L.E. cells and
antinuclear antibodies .6
In m any instances, adm inistered drugs
alter a m etabolic pathw ay and directly
produce changes in biochem ical values.
Insulin adm inistration results in changes
in blood glucose, potassium , phosphorus
and fatty acids. A llopurinol reduces uric
acid by in hibiting th e enzym e, xanthine
oxidase; other drugs, e.g., azoserine and
m ethotrexate, do so by preventing its
biosynthesis. H ydrochlorothiazide in ­
creases uric acid retention by decreasing
its tu bu lar excretion. Oral contraceptives
have a m arked effect on plasm a glucose,
fatty acids and grow th horm one levels .16
E strogen-progestin oral contraceptives
produce increases in serum iron, iron-
bind ing capacity, transferrin, ceruloplas­
m in and cop per .18 T hese effects on en ­
docrine functions are qu ite m arked as in ­
dicated by m easurem ent of the related
biochem ical constituents (table IV ).12
Som e drugs induce unexpected side ef­

Plasma cortisol 15.0 ± 4.0 yg/dl 40.0 ± 11 yg/dl fects un related to th eir therapeutic ac­
(8:00 A.M.) tions. Inheritance of hem oglobins differ­
Serum thyroxine
Urinary 17-OH
6.6 ± 1.4 yg/dl
4.6 ± 1.1 mg/d
9.4 ± 1.7 yg/dl
2.6 ± 0.9 mg/d ing in structure from norm al hem oglobin
corticosteroids
Estrogens, total 40.0 ± 18 yg/d
A is w ell described. All types of hem o­
globin are oxidized to m ethem oglobin by a
26.0 ± 7.4 yg/d
(urine)
Vanilmandelic
acid (urine)
3.5 ± 1.6 mg/d 3.3 ± 1.6 mg/d
w ide range of agents and about 1 percent
o f hem oglobin present in the blood of
*Lucis, O.J. and Lucis, R. : Bull. WHO 46:443, 1972. norm al peo ple is in this form. M any drugs
 DRUG INTERFERENCE IN LABORATORY TESTING 267
slightly increase th e am ount of m ethem o- TABLE VI

globin, even in norm al individuals, b u t Drugs Inducing Hepatic Microsomal Enzymes

induce a striking and som etim es fatal

m ethem oglobinem ia in susceptible pa­ Phenylbutazone Barbiturates

tients. T hese drugs include chlorates, Aminopyrine Cortisone Glutethimide

Chlordiazepoxide
sulfonam ides, nitrites, quinones, acetan- Diphenylhydantoin
Carbutamide
Testosterone
Norethynodrel
ilid and acetophenetidin. A sim ilar p h en­
om enon occurs w ith prim aquine sensitiv­
ity. Susceptible patients have an in herited tisol and decrease the concentration of
defect in red cell glucose 6 -phosphate de­ cortisol in th e plasm a.
hydrogenase (G 6 -PD ) an d develop a se­ A dverse side reactions m ay also occur
vere hem olytic anem ia w hen exposed to w ith pharm acologically active drugs.
prim aquine. M any drugs have b een associated w ith
A nother abnorm al drug response is inducing abnorm al liver, renal an d p u l­
porphyria. A cute porphyria on exposure m onary function .10 T hese drug-test ef­
fects are
to drugs can be caused by sudden m as­ ognized. D rugs in this unexpected and should be rec­
sive induction o f deltaam ino levulinic m ethyltestosterone, reserpine, group include
acid synthetase in hepatic m itochondria phenace-
w hich results in uncontrolled form ation m ide, oxyphenylbutazone, anesthetics
of porphobilinogen and its m etabolites. and a variety of cancer chem otherapeutic
agents.
S usceptibility is in herited as an au­
tosom al dom inant trait and occurs even in D rug-D rug Interactions
heterozygotes. T he nature o f th e m olecu­ D rugs w hich in dep end ently have little
lar defect is unclear and presum ably lies effect on laboratory tests m ay interact to
in the repression m echanism for the gene produce a significant alteration o f test
controlling form ation of the enzym e pro­ values. In table V II are presented several
tein. E xposure to any o f the drugs listed drug interactions in diabetic hum an sub­
in table V results in further m arked dere­ jects w hich can affect an apparent test
pression of enzym e synthesis and severe result .15
porphyria. T he adm inistration of clofibrate to a p a­
In table VI are listed several drugs in ­ tien t taking warfarin w ill potentiate the
ducing hepatic m icrosom al enzym es .5 anticoagulant effect of w arfarin by dis­
T hese enzym es can m etabolize th e drug placing it from its protein bind ing site .7
as w ell as other substrates. Barbiturates, T his interaction w ill cause a significant
griseofulvin and glutethim ide induce en ­ increase in the prothrom bin tim e test
zymes w hich m etabolize coum arin and used to regulate w arfarin adm inistration.
p h enindion e derivatives and thus reduce D isplacem ent o f drugs from th eir b inding
th eir anticoagulant activity. D iphenylhy- sites is a com m on m echanism by w hich
dantoin and phenylbutazone stim ulate drug-drug interactions result in unex­
cortisol hydroxylase activity and increase p ected laboratory data. After absorption,
the urinary excretion of B-hydroxy cor- about 50 to 80 percent of salicylate is
bound to serum album in, from w hich it
T ABLE V
d isp laces o th e r su b stan ces such as
Drugs Inducing Marked
bilirubin and thyroxine. O ther drugs such
as coum arin may also be displaced w ith a
De-repression of Enzyme Synthesis

Chloroquine Diallybarbiturate sudden change in prothrom bin tim e.

Aminopyrine Allylisopropylacetylurea D rug-drug interactions m ay also cause
Sulfonamides Hexachlorobenzene
enzym e induction. Ethchlorvynol, glu-
268 FORMAN AND YOUNG

T A B L E VII

Drug Interactions Reported in Diabetic Subjects

Drug Interaction Hypoglycemic Drug Reaction

Alcohol Insulin Inhibition of gluconeogenesis

Sulfonylurea
Alcohol Phenformin Lactic acidosis
Bishydroxycoumarin Chlorpropamide Decrease in excretion or metabolism of hypoglycemic agent
Guanethidine Insulin Decrease in insulin dosage needed to control patient
Oxytetracycline Insulin Decrease in insulin dosage needed to control patient
Phenothiazine Insulin Increase in insulin dosage needed to control subject
Propranolol Insulin Decrease in insulin dosage needed to control subject

tethim ide and haloperidol are know n to
in h ib it the effectiveness of w arfin therapy
by this m echanism .7 T hese drug-drug
interactions may result in a redic ed pro-
tlr on b in tin e. E nzyn e inhibition is
another resu lt of drug-drug interaction
an d the in paim e n t of the hepatic glicur -
onyl transferase system by phenothiazine
derivatives is a good exam ple. W henever
several dru gs are adn in istered c oncug
rently to a patient, th eir com bined effect
on laboratory results should be carefully
considered.
E ffectiveness of C om puterized D rug
Interference F ile
T he com puterized drug interference
file has b e e n used in tw o m odes. In one,
possible interactions are listed in re­
sponse to direct queries (the role for
w hich it was originally designed). In the
other, th e file has been used to provide
autom atic interpretation of effects of
drugs on tests. In this m ode, the file is
used to provide a report alerting a physi­
cian to a possible interaction betw een a
drug and a test (figure 1). W ithout a com ­
puterized hospital inform ation system,
w hich could be accessed to provide in­
form ation about a patien t’s clinical state
and nontherapeutic-drug procedures, the
drug file cannot be com pletely effective
in providing explanations for changes in
laboratory data. Its role m ust be that of a
w arning system to highlight possible
causes o f changes in test values w hich
can be accepted or rejected b y the pa­
tien t’s physician on th e basis of his clini­
cal ju d g m en t
O ur experience in a university teaching
hospital, in w hich over 10,000 patient-
days w ere m onitored, indicated th at the
drug file provided the correct explanation
for changes in laboratory data in approx­
im ately 21 p ercent of all the occasions in
w hich a report was produced .21 A report,
sim ilar in con ten t and form at to an entry
in the m aster file ,20 was generated w hen
an abnorm al test resu lt was produced and
one of th e adm inistered drugs had b een
described as causing th e effect. T he yield
of correct explanations w ould undoub­
tedly be increased by elim ination of ef­
fects th at w ere unlikely to arise in hospi­
tal practice, e.g., effects ow ing to over­
doses or toxic effects of drugs. To m ake it
appropriate for on-line use in any particu­
lar hospital, the file should be m odified
to elim inate these effects. T he only
m ethodological interferences that should
be in clu ded are those involving the pro­
cedures in use in the hospital laboratory.
T he file is being m odified for use in the
autom atic w arning role in a com m unity
hospital to determ ine if it can provide a
useful service for physicians w ith a differ­
ent orientation from those in a university
hospital.
In the off-line m ode of use of the drug
file, the data-base, stored in a tim e-shared
com puter, is interrogated through a re­
m ote device such as a cathode-ray term i-
 DRUG INTERFERENCE IN LABORATORY TESTING 269
DRUG EFFECTS 10/23/75
PATIENT ID. 086-24-095
PATIENT NAME ROBERT STAR
ROOM NUMBER 4102
DOCTOR GUTHRIE

DRUG: HEPARIN

CLOTTING TIME INC BLOOD (WHOLE) PHYSIOLOGICAL EFFECT

CONCENTRATION RELATED EFFECT REF: 0704

FACTOR IX DEC BLOOD (WHOLE) PHYSIOLOGICAL EFFECT

REPORTED EFFECT REF: 0384

FACTOR V DEC BLOOD (WHOLE) PHYSIOLOGICAL EFFECT

CONCENTRATION RELATED EFFECT REF: 0384

FACTOR XI DEC BLOOD (WHOLE) PHYSIOLOGICAL EFFECT

CONCENTRATION RELATED EFFECT REF : 0384

PLATELET COUNT DEC BLOOD (WHOLE) PHYSIOLOGICAL EFFECT

F igure 1. Report alert- REPORTED EFFECT FOLLOWING I.V. INFUSIONS REF: 0656
ingphysicianto druginter-
ferences in laboratory test­ PITT INC BLOOD (WHOLE) PHYSIOLOGICAL EFFECT

ing. CONCENTRATION RELATED EFFECT REF : 0704

THROMBIN TIME INC BLOOD (WHOLE) PHYSIOLOGICAL EFFECT

RELATED TO CONC OF CIRCULATING HEPARIN REF: 0704

THROMBOPLASTIN GEN DEC BLOOD (WHOLE) PHYSIOLOGICAL EFFECT

ABNORMAL RESPONSE (INHIBITION) REF : 0384

AMMONIA INC PLASMA ANALYTICAL EFFECT

CONTAINS VARIABLE AMOUNTS OF AMMONIUM SALTS REF: 0181

CORTICOSTEROIDS INC PLASMA ANALYTICAL EFFECT

IF CONTAMINATED BY IMPURITIES REF: 0524

INSULIN DEC PLASMA ANALYTICAL EFFECT

EFFECT IN HEPARINIZED PLASMA AND SERUM REF: 0709

INSULIN INC PLASMA ANALYTICAL EFFECT

SPURIOUSLY HIGH VALUES REPORTED FOR IMMUNOASSAY REF : 0064

PROTHROMBIN TIME INC PLASMA PHYSIOLOGICAL EFFECT

CONCENTRATION RELATED EFFECT REF : 0704

TSH DEC PLASMA PHYSIOLOGICAL EFFECT

INTERFERES WITH THYROXINE BINDING TO PROTEIN REF: 0502

nal. T he questions th at may be asked in­
clude all the effects of a drug, all the
drugs that affect a test or, m ore specifi­
cally, does a particular drug affect a par­
ticular test procedure by a particular
m echanism . In each of these situations it
is possible to list th e appropriate litera­
ture reference. T he search procedure has
b een designed in an interactive m ode so
th at even an individual w ho has never
used it may obtain an explanation for a
particular problem , b u t the exp erienced
searcher can by-pass th e longer interac­
tive search routine. This m ode of opera­
tion is in use only at the N ational Insti­
tutes o f H ealth, (NIH ) and a sim pler
procedure is used in E vanston H ospital.
T he m ost im portant use of a com puter
in setting up the CLA U D E (Com puter
L isting o f A bnorm al and U sual D rug E f­
fects) concept may be th at of a text editor
and sorter. Scanning a printout is m uch
m ore efficient than searching the file in
the com puter, except for any inform ation
that is not yet available on a printout. It is
our intention to reproduce printouts of
270 FOBMAN AND YOUNG
th e file in a journal w ith a w ide circula­
tion to th e appropriate audience w h en a
significant am ount o f new inform ation
has b e en added to th e m aster-file. T he
second edition has recently b een p u b ­
lish ed .22 It includes som e inform ation on
th e probabilities of certain effects occur­
ring, as w ell as an indication of the con­
centration of drug at w hich th e effects
occur, at least for the m ethodological
effects.
T he file is used routinely in the
laboratory at N IH in an attem pt to explain
abnorm al te st resu lts. T he re sid e n t
physicians affiliated w ith th e clinical
chem istry service discuss the results w ith
the patient-care physicians to determ ine
if the results w ere due to the patien t’s
clinical state or to a drug effect. This
close m onitoring of test results has led to
recognition of deficiencies in w hat is b e ­
lieved are specific enzym atic procedures
for the m easurem ent of glucose and uric
acid. L ikew ise, th e guaiac procedure for
occult blood in feces was found to yield
false negative results un d er certain cir­
cum stances. T his has prom pted the de­
velopm ent of a m ore specific procedure
(Jaffe e t al. unpublished).
T he file m ay be q u eried in response to
questions from clinical staff at N IH , to
physicians and to laboratory scientists
throughout the country w ho subm it th eir
problem s by letter or telephone. T he file
has b een u sed to provide inform ation for
a pharm aceutical m anufacturing com ­
pany preparing a new drug application to
th e F ood and D rug A dm inistration. For
the latter organization, th e file has b een
u sed as a background resource for pro­
duct class standards.
O n m any occasions, th e file has pro­
vided inform ation about effects of drugs
o f w hich the user was previously una­
w are. U ndoubtedly, this has h elped in
the care of som e patients. Several cases
have b een brought to light in w hich pro­
longed w orkups o f unusual test values
w ere avoided ow ing to the sim ple expla­
nations provided by the file. It is ex­
p ected th at the application o f th e file w ill
be expanded by introducing it in a re­
vised form into several hospitals for on­
line interpretation of data. Also, discus­
sions have b e e n h eld w ith several
different institutions overseas to set up
national centers for dissem ination of in ­
form ation and to provide better m onitoring
of foreign language publications to aug­
m ent th e content of the file.
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