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Pharmacokinetics and bioavailability of an essential oil compound (thymol)

after oral administration

Conference Paper  in  Focus on Alternative and Complementary Therapies · March 2001

DOI: 10.1111/j.2042-7166.2001.tb02833.x

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KOHLERTMEDICINE
AVAILABILITY
HERBAL ET AL
AND PHARMACOKINETICS OF THYMOL
Systemic Availability and Pharmacokinetics
of Thymol in Humans
Claudia Kohlert, PhD, Gernot Schindler, MD, Reinhard W. März, PhD,
Gudrun Abel, PhD, Benno Brinkhaus, MD, Hartmut Derendorf, PhD, FCP,
Eva-Ulrike Gräfe, PhD, and Markus Veit, PhD
Essential oil compounds such as found in thyme extract are
established for the therapy of chronic and acute bronchitis.
Various pharmacodynamic activities for thyme extract and
the essential thyme oil, respectively, have been demonstrated
in vitro, but availability of these compounds in the respective
target organs has not been proven. Thus, investigation of ab-
sorption, distribution, metabolism, and excretion are neces-
sary to provide the link between in vitro effects and in vivo
studies. To determine the systemic availability and the
pharmacokinetics of thymol after oral application to hu-
mans, a clinical trial was carried out in 12 healthy volunteers.
Each subject received a single dose of a Bronchipret® TP tab-
let, which is equivalent to 1.08 mg thymol. No thymol could
be detected in plasma or urine. However, the metabolites
E ssential oil compounds such as found in thyme ex-
tract are frequently used for the therapy of chronic
and acute bronchitis. For these indications, several
clinical trials have been carried out. 1-4 Various
pharmacodynamic activities for thyme extract and the
essential thyme oil, respectively, have been demon-
strated in vitro,5-7 but bioavailability of thyme oil ingre-
dients has not been proven.
From the German Central Institute for Pharmaceutical Research (Dr.
Kohlert, Dr. Gräfe, Dr. Veit), Sinzig, Germany; Department of Medicine I,
Department of Complementary Medicine (Dr. Schindler, Dr. Brinkhaus),
Friedrich-Alexander University, Erlangen-Nürnberg, Erlangen, Germany;
Bionorica AG (Dr. Abel, Dr. März), Neumarkt/Opf., Germany; and Col-
lege of Pharmacy (Dr. Derendorf), University of Florida, Gainesville. Sup-
ported by Bayern Innovativ, government funds, and Bionorica AG. Sites
where the study was performed include the following: German Central In-
stitute for Pharmaceutical Research; Friedrich-Alexander University,
Erlangen-Nürnberg; and Bionorica AG. Dedicated to Professor Otto
Sticher on the occasion of his 65th birthday. Submitted for publication Sep-
tember 28, 2001; revised version accepted March 3, 2002. Address for
reprints: Dr. Markus Veit, German Central Institute for Pharmaceutical Re-
search, Kranzweiherweg 10, 53489 Sinzig, Germany.
J Clin Pharmacol 2002;42:731-737
HERBAL MEDICINE
thymol sulfate and thymol glucuronide were found in urine
and identified by LC-MS/MS. Plasma and urine samples were
analyzed after enzymatic hydrolysis of the metabolites by
headspace solid-phase microextraction prior to GC analysis
and flame ionization detection. Thymol sulfate, but not
thymol glucuronide, was detectable in plasma. Peak plasma
concentrations were 93.1 ± 24.5 ng ml –1 and were reached af-
ter 2.0 ± 0.8 hours. The mean terminal elimination half-life
was 10.2 hours. Thymol sulfate was detectable up to 41 hours
after administration. Urinary excretion could be followed
over 24 hours. The amount of both thymol sulfate and
glucuronide excreted in 24-hour urine was 16.2% ± 4.5% of
the dose.
Journal of Clinical Pharmacology, 2002;42:731-737
©2002 the American College of Clinical Pharmacology
Essential oils are mixtures of lipophilic, liquid, vola-
tile, and often terpenoid compounds present in higher
plants. More than 3000 compounds have been de-
scribed so far.8 A broad variety of pharmacological ac-
tivities of essential oils and their constituents have
been investigated for potential use in medicine.9 One
particular area of use for essential oils is respiratory
medicine, where the oils of pine, eucalyptus, and
thyme have a sound tradition and several clinical stud-
ies have provided evidence of efficacy.1-4,10-12 In particu-
lar, 1,8-cineol, originally a component of eucalyptus
oil,10,12 and standardized myrtol2,4,11 have been sub-
jected to pharmacological and clinical studies focusing
on respiratory diseases. Thyme extracts, which are
very popular in Germany for these disorders, have only
a small record of clinical studies, but there is no dispute
about their efficacy.1,3 Thyme extract products have
shown clinical efficacy against acute bronchitis in
comparison to synthetic compounds,3 as well as vari-
ous activities in pharmacological assays.
A dose-dependent anti-inflammatory effect of
thyme extract was shown in carrageenin-induced
731
 KOHLERT ET AL
edema in rat paws.5 Antimicrobial activity against sev-
eral gram-positive and gram-negative bacteria was
shown for different thyme oils.7,13 By means of a
bioimpedometric method, the bacteriostatic activity of
thyme oil was determined.7 The essential oil of
thyme—applied in concentrations from 50 ppm to 400
ppm—resulted in a reduction in the rate of growth of
different bacteria. Concentrations of 200 ppm achieved
more than 50% inactivation of the majority of microor-
ganisms tested.7 Antibacterial activity against respira-
tory tract pathogens by gaseous contact was investi-
gated recently.14 Petri dishes with thyme oil or thymol
were placed in an airtight box, and inhibitory concen-
trations were measured.
In addition, antiviral activities against influenza A
virus and respiratory syncytial virus were found for
thyme extract in the plaque reduction test.6 Recently,
antioxidant effects of thyme oil and thymol in various
rat tissues were reported.15
However, the clinical relevance of these activities
depends on the systemic availability of these com-
pounds in the respective target organs. Thus, investiga-
tion of absorption, distribution, metabolism, and excre-
tion would provide a significant link between in vitro
effects and in vivo efficacy. They may also be important
in context of the safety of herbal medicinal products.16
Pharmacokinetics of most natural compounds such as
thymol have not yet been investigated satisfactorily.
For several monoterpenoid and phenylpropanoid
compounds, there is a large amount of experimental
data, but—especially with respect to humans—
pharmacokinetic data are lacking.16
To evaluate whether thymol, the main compound of
the essential oil of thyme, can contribute to the clinical
efficacy observed for a preparation containing thyme
extract (Bronchipret® TP tablets), a bioavailability
study after oral administration of a single dose was car-
ried out. This study should also provide preliminary
data for further dose-finding studies and for the design
of multiple-dose studies.
SUBJECTS AND METHODS
Subjects
The study was carried out at the Department of Medi-
cine I, Department of Complementary Medicine,
Friedrich-Alexander University, Erlangen-Nürnberg
(Erlangen, Germany).
Twelve healthy male volunteers were recruited for
the study after complete clinical examination. Routine
blood and urine laboratory tests were performed. Mean
age was 29.5 ± 6.74 years (mean ± SD), and mean body
732 • J Clin Pharmacol 2002;42:731-737
mass index was 24.6 ± 2.0 kg m–2 (mean ± SD). Subjects
were not allowed to use any medicine during the study.
All subjects signed an informed consent form accord-
ing to good clinical practice (GCP) guidelines. The pro-
tocol was approved by the ethics committee of the Uni-
versity of Erlangen, Germany.
Study Design
Each subject received a single dose of Bronchipret® TP
tablets containing 60 mg of primrose dry extract
(6.0-7.0:1; extracted by ethanol 47% (v/v)) and 160 mg
of thyme dry extract (5.9-10.0:1, extracted by ethanol
50% (m/m)), which was batch-specific equivalent to
1.08 mg of thymol. The subjects were fasted at the time
they received the medication. They stayed in the clinic
for the first 15 hours of the study and returned to the
clinic for regular blood sampling visits. Prestudies in-
dicated that long sampling times would be necessary to
cover the elimination phase completely. Therefore, a
sampling period of 72 hours was chosen. During the
entire time, they were on an essential oil-free diet, and
they were not allowed to apply any cosmetics (e.g.,
toothpaste, aftershave, etc.) containing essential oil
compounds to avoid interference with any other essen-
tial oil compounds. Therefore, the subjects were
handed out a list with food and cosmetics they were not
allowed to eat and apply during the time of the study
period.
Collection of Blood
and Urine Samples
Venous blood samples (9 ml per blood sample) were
collected into EDTA tubes once before subjects were
administered the medication and 0.25, 0.5, 0.75, 1, 1.5,
2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 31, 38, 48,
55, 62, and 72 hours after administration. Blood was
centrifuged for 10 minutes at 4000 × g. The supernatant
plasma was transferred into reaction cups in aliquots of
0.5 ml, and 20 µl acetic acid 0.58 M were added to each
aliquot for stabilization. The plasma was stored at
–20°C until analysis. Urine was collected in plastic bot-
tles in intervals of 0 to 3, 3 to 6, 6 to 9, 9 to 14, 14 to 24,
24 to 31, 38 to 48, 48 to 55, 55 to 62, and 62 to 72 hours.
An aliquot of 50 ml of each sample was mixed with 0.1 g
ascorbic acid as antioxidant and stored at –20°C until
analysis.
Analytical Methods
For the determination of total concentration of thymol,
thawed plasma samples were analyzed after enzymatic
 AVAILABILITY AND PHARMACOKINETICS OF THYMOL
hydrolysis of conjugated thymol by headspace
solid-phase microextraction (HS-SPME) prior to gas
chromatographic analysis.17 For urine analysis, only 20
µl of acetic acid 0.58 M compared to 50 µl used in the
plasma method were necessary to adjust to pH 5 be-
cause ascorbic acid was added before the samples were
frozen. In addition, adaptation of the SPME extraction
time to 25 minutes instead of 35 minutes for plasma
analysis was performed, which is due to the different
matrix.
Validation of the methods was performed according
to the FDA Draft Guidance for Industry No. 2578
(Bioanalytical Methods Validation for Human Studies).
For both plasma and urine analysis, the international
acceptance criteria were in the ranges required. At the
limit of quantification (LOQ), within-day precision of
the plasma and urine assay was below 19% and 12%
(coefficient of variation [CV]), respectively, and below
5.6% (plasma) and 7.2% (urine) at higher concentra-
tions. Accuracy was below 9% for plasma and below
13% for urine. Stability of both plasma and urine sam-
ples was given over 12 weeks at –20°C. The lower limit
of quantification for plasma analysis was 8.1 ng ml–1
and for urine 10.9 ng ml–1.
Plasma samples were analyzed in 12 runs and the
urine samples in 5 runs. Each run was checked for lin-
earity by a separate calibration curve. Precision and ac-
curacy were controlled by running six external quality
control samples (spiked blank plasma and urine sam-
ples with reference compounds) covering the whole
range.
The identification of phase II metabolites and the de-
termination of free thymol in both plasma and urine
were carried out exemplarily in 2 subjects each.
For identification of the phase II metabolites,
LC-MS/MS measurements were performed by A&M
(Laboratory for Investigations in Analytics and Metab-
olism, Bergheim, Germany). Prior to LC-MS/MS (ion-
ization mode: ESI negative), the following sample
preparation procedures were applied. After addition of
550 µl acetonitrile to 550 µl plasma, the solution was
vigorously shaken for 20 seconds and centrifuged at
7800 × g for 4 minutes. The solvent was removed under
nitrogen stream at 40°C. The residue was dissolved in 5
µl acetonitrile and 45 µl 2 mM ammonium acetate by
ultrasonication. After centrifugation at 7800 × g for 4
minutes, the supernatant was used for HPLC analysis.
For urine sample preparation, 4 ml urine were acidi-
fied with 8 µl formic acid; 14 ml ethylacetate were
added, and the samples were shaken for 2 minutes. For
separation of the organic and aqueous phase, the sam-
ples were centrifuged at 7800 × g for 4 minutes, and the
supernatant was evaporated under nitrogen stream at
HERBAL MEDICINE
40°C. The residues were dissolved in 12 µl acetonitrile
and 108 µl 2 mm ammonium acetate by means of
ultrasonication and used for HPLC analysis.
Determination of free thymol in plasma was carried
out by HPLC with a 12-channel coulometric array de-
tector at the German Institute of Nutrition (Bergholz-
Rebrücke, Germany). To 400 µl of plasma (pH 5), 50 µl
internal stock solution (o-Cresol, 4 µg ml–1), 50 µl water,
and 500 µl methanol were added, vortexed, and centri-
fuged for 10 minutes at 7800 × g. The supernatant was
used for HPLC analysis.
Determination of free thymol in urine was carried
out by GC-MS. n-Heptane (250 µl) was added to 500 µl of
urine (pH 5) and vortexed for 20 minutes at 350 rpm.
The supernatant was used for GC-MS analysis.
Data Analysis
Pharmacokinetic data were determined by non-
compartmental analysis using Microsoft Excel based
on the equations given by Gibaldi and Perrier.18 The
maximum observed plasma concentration Cmax and the
time to reach Cmax (tmax) were determined directly from
the data. The AUC0 → clast was calculated using the linear
trapezoidal rule. The apparent terminal elimination
half-life was determined by linear regression of the ter-
minal phase of the semilogarithmic plasma concentra-
tion versus time profiles. The mean absorption time
(MAT) was calculated from 1/ka, which was obtained
from ke and tmax by the Excel Solver function from tmax =
ln(ka/ke)/(ka – ke).
RESULTS
Free thymol could not be detected in human plasma.
By means of LC-MS/MS analysis, only thymol sulfate
but not the glucuronide was identified in human
plasma (reference compound proved feasibility) (Fig-
ure 1). The plasma concentration versus time curves of
thymol sulfate (measured by LC-MS) and total thymol
concentrations after enzymatic hydrolysis of plasma
(measured by HS-SPME) showed parallel profiles (Fig-
ure 2). Hence, the quantification of thymol in plasma
was based on the total thymol concentration after enzy-
matic hydrolysis of the sulfate.
No free thymol was found in urine either. Instead,
two phase II conjugates were identified by LC-MS/MS
as thymol sulfate and thymol glucuronide (Figure 1).
The ratio of peak areas of thymol sulfate and thymol
glucuronide was constant over the different urine frac-
tions (Figure 3).
The time course of the total thymol concentrations
in human plasma is shown in Figure 4. Pharma-
733
 KOHLERT ET AL

thymol sulfate
thymol glucuronide

peak area
RO

Compound R 3 6 9 14
time [h]

-------------------------------- ------------------------------ Figure 3. Cumulative renal excretion of thymol sulfate and thymol
glucuronide in 1 subject.

thymol H—

thymol sulfate plasma concentration versus time profile was biphasic,

HO3S subdivided into a distribution phase and a slow termi-
nal elimination phase beginning at about 10 hours after
administration and lasting up to an average of 38 hours.
thymol glucuronide HOOC Elimination half-life was calculated to be 10.2 ± 1.4
O hours (mean ± SD) (Table I).
HO In urine, the elimination of thymol conjugates was
HO
OH detectable for the first 24-hour interval, with most be-
ing eliminated after 6 hours. The combined amount of
Figure 1. Structures of thymol, thymol sulfate, and thymol
glucuronide.
both thymol sulfate and glucuronide excreted in
24-hour urine was 16.2% ± 4.5% of intake. The renal
clearance was calculated to be 0.271 ± 0.7 L h–1.

DISCUSSION
140
thymol sulfate [response/250000]

120
Thymol was present in human plasma only as thymol
100 sulfate. Hence, the quantification of thymol was based
Cp [ng.mL-1]

80 on the thymol concentration obtained after enzymatic

60
40
20
0 quickly. Considerable plasma concentrations of thymol
0 1
Figure 2. Thymol plasma concentration determined after enzy-
matic hydrolysis of plasma ( ) and thymol sulfate measured by
LC-MS in 1 subject ( ).
cokinetic data analysis was performed with only 11
subjects, as thymol was already detected in the blank
samples (plasma and urine) of 1 subject. Thymol was
rapidly absorbed. Thymol sulfate could be detected in
plasma 20 minutes after application. Maximum plasma
levels of 93.1 ± 24.5 ng ml–1 (mean ± SD) were reached
after 1.97 ± 0.77 hours (mean ± SD) (Table I). The
hydrolysis. Intake of one Bronchipret® TP tablet re-
sulted in plasma concentrations that showed the same
profile among all subjects. Thymol was absorbed
2 3 4 5 6 sulfate could already be detected after 20 minutes. This
t [h] fast absorption indicates that thymol is mainly ab-
sorbed in the upper part of the gut. This confirms previ-
ous observations made by Somerville et al19 with
ileostomy patients. In this study, the renally excreted
amount of menthol after oral intake of peppermint oil
by ileostomy patients was only 11% less compared to
healthy volunteers. After oral application of 1,8-cineol
and α-pinene, these compounds were detectable after
10 to 30 minutes in plasma as well.20,21 This fast absorp-
tion of essential oil compounds might have been fa-
vored by the small size and the lipophilic characteris-
tics of the molecules.
Maximum plasma concentrations of 93.1 ng ml–1 were
reached after 1.97 hours (Table I), which is in accordance

734 • J Clin Pharmacol 2002;42:731-737

 AVAILABILITY AND PHARMACOKINETICS OF THYMOL

Table I Pharmacokinetic Data of Total Thymol Absorption and Elimination

in Human Plasma after Single Oral Administration of One Bronchipret® TP Tablet
Mean SD Minimum Value Median Maximum Value Geometric Mean Number

Dose (mg) 1.08

Cmax (ng/ml) 93.11 24.47 55.90 99.01 125.82 90.04 11
tmax (h) 1.97 0.77 0.80 2.03 3.13 1.81 11
t1/2 (h) 10.2 1.4 8.3 9.9 12.9 10.1 11
AUC0 → clast (ng h/ml) 837.3 278.5 456.7 835.8 1281.6 793.6 11
MRTabs (h) 12.6 2.1 8.1 12.5 15.2 12.4 11
MAT (h) 0.53 0.04 0.46 0.54 0.59 0.53 11
CLtot/f (L/h) 1.2 0.3 0.8 1.1 1.8 1.2 11
Vdss/f (L) 14.7 5.1 6.1 13.8 23.3 13.9 11
Vdarea/f (L) 17.7 5.6 10.8 17.2 29.5 16.9 11
Cmax, peak plasma concentration; tmax, time to reach Cmax; t1/2, elimination half-life; AUC0 → clast, area under the concentration-time curve from time 0 to
clast; MRTabs, mean residence time after extravascular administration; MAT, mean absorption time; CLtot/f, total body clearance with respect to unknown
bioavailability f; Vdss/f, volume of distribution at steady state with respect to unknown bioavailability f; Vdarea/f, volume of distribution during the elimination
phase with respect to unknown bioavailability f.

pounds investigated.22-25 The terminal elimination

1000 phase set in after 10 to 12 hours, and thymol could be
mean
detected up to an average of 38 hours. Elimination
median
100
half-life was determined to be 10.2 hours (Table I).
Cp [ng .mL -1]

Other compounds such as 1,8-cineol and α-pinene

showed elimination half-lives of 3.6 and 5.8 hours, re-
10
spectively.20,21 Although plasma levels were detectable
up to an average of 38 hours, the renal elimination of
1 thymol conjugates was completed within 24 hours. This
0 5 10 15 20 25 30 35 40 discrepancy might be due to the fact that very small
tim e [h] amounts of renally eliminated thymol conjugates could
not be quantified any more after 24 hours (< LOQ).
The fact that thymol sulfate is eliminated slowly can
120 also be deduced from the small clearance (Cltot/f) of 1.2
100
mean
L h–1. The renal clearance of 0.271 L h–1 indicates high
median
80
protein binding and/or reabsorption in the kidney, re-
Cp [ng.mL-1]

spectively. The volume of distribution (Vdss/f) of 14.7

60
L indicates that thymol sulfate stays mainly in the
40 extracellular space (Table I). The bioavailability of
20 thymol sulfate after administration of thymol is at least
16%, because 16% of the dose administered was ex-
0
0 5 10 15 20 25 30 35 40
creted into the urine as thymol conjugates. However,
time [h] since Vdss/f is only 14.7 L, a much larger number for f is
likely.
Figure 4. Thymol concentration (after enzymatic cleavage) in Thymol was present in human plasma only in its
plasma (mean ± SD; median) of 11 volunteers after administration of conjugated form. Our LC-MS/MS experiments gave ev-
®
one Bronchipret TP tablet. idence only for thymol sulfate; the glucuronide was not
detected. However, for other phenolic compounds,
there is evidence for both metabolites. After oral appli-
with the tmax from other essential oil compounds after cation of a mixture of phenol, guaiacol, p-cresol, and
oral intake.20,21 Thymol plasma concentrations— after creosol (15-32 mg each), formation of glucuronide
enzymatic hydrolysis of thymol sulfate—showed a and—except for creosol—sulfate was observed in se-
biphasic profile like most of the essential oil com- rum.26 The absence of thymol glucuronide in plasma

HERBAL MEDICINE 735

 KOHLERT ET AL
could be the result of lower activity of hepatic UDP-
glucuronyltransferase compared to sulfotransferase.
Thus, conjugation to sulfuric acid and glucuronic acid
would compete, and only after application of much
higher doses, formation of glucuronide could be ob-
served.26 Free thymol was not present in human
plasma, which is in accordance with investigations
from Ogata et al.26 Despite much higher doses of phe-
nols, only a small amount of free phenols could be de-
tected in serum. The data available so far indicate that
thymol is systemically available only as thymol sulfate.
In urine, both thymol glucuronide and thymol sul-
fate were present, which confirms previous observa-
tions made by Takada et al.27 After oral application of
thymol to humans and rats, both metabolites were
identified in urine, but confirmation of structure by MS
was lacking. Phenol applied intravenously to mice re-
sulted in excretion of both metabolites, with sulfate be-
ing the main metabolite. Increasing dose shifted the ra-
tio from sulfate toward glucuronide.28 For phenol,
guaiacol, p-cresol, and creosol, formation of both con-
jugates—except for creosol—was observed.26
Free thymol was not found in urine. After oral appli-
cation of 500 mg menthol to volunteers, no free men-
thol could be detected in urine.29 Unconjugated phe-
nol, guaiacol, p-cresol, and creosol were found in urine
only in small amounts, although the dose was more
than 15 times higher than applied in our study.26
Data available so far indicate that—despite its ab-
sence in plasma—thymol glucuronide is eliminated
renally. For other compounds (e.g., probenecid), the
presence of the glucuronide in urine was proven, al-
though it was not detected in plasma.30,31 In the case of
thymol, thymol sulfate could be reabsorbed in the
proximal tubule after glomerulary filtration. Cleavage
to thymol could be achieved by the activity of
arylsulfatases, which was proven for human kidney tis-
sue.32 On the other hand, it is conceivable that the
cleavage to thymol is achieved by enzymes located at
the luminal brush border.33,34 Thus, thymol could be
subsequently reabsorbed.
Glucuronidation of thymol could be performed by
UDP-glucuronyltransferases followed by secretion into
the proximal tubule. Investigations in human kidney
microsomes point to this mechanism. Although the
liver is considered the most important organ for
biotransformation, recently, kidney microsomes have
demonstrated more effective glucuronidation of phe-
nolic compounds than liver microsomes or intestinal
microsomes.35,36 Extrahepatic glucuronidation was also
proven for morphine37 and for propofol,35 which is
structurally similar to thymol. In addition, renal
736 • J Clin Pharmacol 2002;42:731-737
glucuronidation of paracetamol,34 1-naphtol,38 and
4-dimethylaminophenol39 was demonstrated by means
of the isolated perfused rat kidney. Furthermore, vari-
able activities of UDP-glucuronyltransferases were
demonstrated for different tissues.36 The constant ratio
of sulfate and glucuronide over the different urine frac-
tions supports the hypothesis of renal cleavage of
thymol sulfate with subsequent conjugation to
glucuronic acid. However, to confirm this hypothesis,
further investigations concerning the mechanism of re-
nal metabolism are necessary.
The data available so far indicate that a pharmaco-
logical effect observed in vivo after oral administration
of a preparation containing thyme extract would be due
to thymol sulfate. However, the pharmacodynamic ef-
fects of this conjugate have not been investigated yet.
The pharmacodynamic effect is not necessarily exerted
by conjugates present in plasma as they may be cleaved
at the site of action by sulfatases. Activity of this group
of enzymes has been proven in human lung tissue for a
number of model compounds.40 Thus, pulmonary
elimination of thymol despite the absence of free
thymol in human plasma could be explained.41 This
way, free thymol could be effective at the target organ
respiratory system. Evidence of cleavage of sulfate to
thymol would provide a further link between in vitro
and in vivo results. In addition, the pharmacodynamic
activity of potential phase I metabolites of thymol as
observed in rats42 would be of great interest for under-
standing its clinical efficacy.
Dedicated to Professor Otto Sticher on the occasion of his 65th
birthday.
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