Terbinafine in hair-samples 
Clinica/ and /aborato,y study 
TERBINAFINE LEVELS IN HAIR-SAMPLES 
OF CHILDREN WITH MICROSPORUM CANIS 
SCALP INFECTION 
V. Dragoš and L. Zaletel-Kragelj 
ABSTRACT 
Eighteen children, aged 2-11 years, with Microsporum canis scalp infection were treated with terbinafine 
orally for 6-16 weeks according to body weight. We studied the levels of terbinafine in the hair samples with 
HPLC (high-pressure liquid chromatography) at the end of treatment and again 1 and 2 weeks later. Hair 
samples were obtained by shaving the same area of the scalp. The cultures were made simultaneously. The 
concentration of terbinafine expressed in ng/lOmg of hair weight was correlated with the result of culture 
(positive-negative ). Eleven of 18 children had all cultures negative and the treatment was successful. The 
median value of terbinafine concentrations were 337ng/10mg of hair, at the end of the therapy, 378ng/10mg 
hair one week later, and 56ng/10mg hair two weeks later. Seven of 18 children had all cultures positive and 
treatment was not successful. The median values of terbinafine concentrations were 15ng/10mg of hair at the 
end of treatment, 5ng/10mg of hair one week later and, 7ng/10mg of hairs 2 weeks later. The concentrations 
of terbinafine were much higher in the group of patients, in whom the therapy was successful, although there 
were no differences in the age, dosage of the drug and duration of the treatment. The reasons for differences 
are not known and may have appeared due to lower sebum output in some patients. Microsporum canis may 
need much higher levels of the systemic antifugals at the site of infection for complete cure. The 
determination of drug levels in the target tissue and its correlation with cultures may be a useful method 
of evaluating the in vivo effect of systemically administered antifungals. 
KEY WORDS 
terbinafine leve!, Microsporum canis, tinea capitis, children 
INTRODUCTION 
Microsporum canis (M.canis) bas been the most 
frequent dermatophyte isolated in Slovenia since 
1989 (1) . The majority of patients with microsporosis 
are children and scalp infection appears in 7% of 
these patients (2). Microsporum canis causes scalp 
acta dennatovenerologica A.P.A. Vol 7, 98, No 3-4 
lesions with slight erythema, scaling and broken-off 
hairs. Typical inflammatory lesions occur rarely. 
Topical treatment of tinea capitis is usually in-
effective; years ago oral griseofulvin was the only 
systemic antifungal agent available for tinea capitis. 
In the treatment of M canis tinea capitis griseofulvin 
in the dosage of 10 mg/ kg/day usually for 23 weeks 
167 
Terbinafine in hair-samples 
was needed (2). Complete cure was achieved after 
6-8 weeks of treatment when higher doses of 15-30 
mg/kg/ day were given (3). 
During the last few years we treated children with 
M. canis scalp infection with oral terbinafine. The 
drug inhibits the synthesis of ergosterol and has 
primarily fungicida! action ( 4). It was found effective 
in the treatment of various dermatophyte skin and 
scalp infections in childhood (5,6). Tinea capitis 
caused by Trichophyton spp. was effectively treated 
after a period of 4 weeks (7,8). However, in scalp 
infection due to M. canis longer treatment or higher 
dosis of oral terbinafine were required for a complete 
cure (5,9). 
Orally given terbinafine is delivered to different 
skin compartments by direct diffusion through dermis 
and epidermis and persist there for severa! weeks 
after the last day of medication (10). The concentration 
of orally given antifungal agent at the site of 
infection is most important for the curative effect of 
the drug. 
In order to evaluate the distribution of orally 
given terbinafine in childrens' hair we studied the 
levels of terbinafine in hair samples of children who 
were treated orally with terbinafine due to M. canis 
scalp infection. 
MATERIALS AND METHODS 
Eighteen children, 13 boys and 5 girls, whose age 
ranged from 2-11 years, with non-inflammatory tinea 
capitis due to M. canis, were treated with oral 
terbinafine according to body weight for 6-16 weeks. 
Terbinafine was given once daily, and the dosage 
was as follows: 62,5 mg/day for children weighing 
less than 20 kg; 125 mg/day for those weighing 20-
40 kg; and 250 mg/day for those weighing more 
than 40 kg. Hair samples were obtained by shaving 
the same area of app. 5 cm2, first at the end of the 
therapy and again one and two weeks later. The 
hair samples were stored in tarred tubes and were 
deeply frozen (-20°C). The levels of terbinafine in 
the hair samples were analyzed by HPLC in CEPHAC-
EUR OPE, 90 Avenue des Hautes de la Chaume, 
BP 28 86281, Saint-Benoit Cedex, France. The cultures 
for dermatophytes were made simultaneously. The 
concentrations of terbinafine were correlated with 
the results of culture analyses (positive-negative ). 
The aim of the study was to determine whether 
there is any difference in the concentration of 
terbinafine in hair samples between the children 
who responded to therapy and those who did not. 
168 
We also wanted to know if terbinafine is present in 
newly grown hair, one and two weeks after the 
discontinuation of the drug. 
RESULTS 
The concentrations of terbinafine in hair samples 
at the end of treatment, at one and two weeks 
follow-up and the statistical evaluation (Mann-Whitney 
U test) are presented in table l. (See Table 1) 
In the group A, 11 out of 18 patients had ali 
cultures negative and treatment was successful. The 
median value of terbinafine concentration was 337 
ng/lOmg hair at the end of therapy, one week later 
it was 378ng/10mg hair, two weeks later it fell to 56 
ng/lOmg of hair. The mean rank of drug concentrations 
was 11.32 at the end of therapy, 11.05 after one 
week and 10.41 after two weeks. 
In group B, 7 out of 18 patients, the cultures 
were positive and treatment was not successful. The 
median value of terbinafine concentration at the 
end of the treatment was 15 ng/lOmg of hair; one 
week later it fell to 5 ng/lOmg of hair and two 
weeks later it was 7 ng/lOmg of hair. The mean 
ranks of the drug concentrations were 6.64 at the 
end of treatment, 7.07 after one week and 8.07 
after two weeks. 
The concentration of terbinafine was more than 
20 times higher at the end of treatment in the 
group A compared to group B. Significant differences 
(Mann-Whitney U test) were present at the end of 
treatment. One and two weeks later mean rank of 
terbinafine concentrations were lower in the group 
of patients in whom the treatment was not successful. 
There were no differences in the age, dosage, and 
the duration of the treatment between the two 
groups of patients. Table 2. 
DISCUSSION 
Terbinafine is a fungicida! drug of the allylamine 
group. It has high in vitro activity against various 
dermatophytes with MIC of 0,002-0,008 mg/ml ( 4). 
In vivo studies are necessary to determine whether 
in vitro susceptibility profiles correlate with clinical 
efficacy (11). 
Terbinafine reaches the stratum corneum and hair 
follicles by passive diffusions from the blood ·stream 
as well as via sebum (12). It may be incorporated 
into the basal keratinocytes and transported to the 
acta de,matovenerologica A.P.A. Vol 7, 98, No 3-4 
Terbinafine in hair-sarnples 
Table l. Distribution of terbinafine concentrations in ng/10mg of hair in children with M. canis scalp infection at 
the end of the treatment (week O), one week (week 1) and two weeks (week 2) afterwards; significance of 
differences (Mann-Whitney U test). In group A the treatment was successful in group B it was not. 
group A 
(n=ll) 
quartile 1 median quartile 3 m!!:!:11. 
week ng/10 mg ng/10 mg ng/10 mg rank 
hairs hairs hairs 
o 11 337 1198 11.32 
1 9 378 1504 11.05 
2 5 56 241 10.41 
stratum corneum during normal celi turnover. High 
levels of terbinafine were found in sebum and it may 
be beneficial in the treatment of mycotic infection of 
the hair follicles. Terbinafine strongly adheres to 
keratin (12). In the study performed by Faergemann, 
healthy adult volunteers, who had been receiving 
250 mg of terbinafine for 7 days, had a drug con-
centration exceeding the MIC for most dermatophytes 
group B 
(n = 7) p 
quartile 1 median quartile 3 !!1El!l 
ng/10 mg ng/10 mg ng/10 mg rank 
hairs hairs hairs 
5 
5 
5 
15 20 6.64 0.070 
5 17 7.07 0.122 
7 12 8.07 0.356 
by a factor of 10-100 in various compartments of the 
skin, 54 days after the last day of medication (10). 
Orally administered terbinafine was distributed in 
the childrens' hair. In children in whom the therapy 
was successful, twenty times higher drug levels were 
present in the hairs at the end of treatment compared 
to the group of patients in whom the therapy was 
not successful. 
Table 2. Significance of differences (Mann-Whitney U test for numerical data and Fisher exact test for count data) 
for age, dosis of terbinafine and duration of treatment in children with M. canis scalp infection which could 
influence the results of treatment: in group A the treatment was successful in group B it was not. 
Group A group B 
(n =11) (n= 7) p 
factor g_uartilel median 
g_uartile3 meanrank g_uartilel median g_uartile3 l!1!fil!rank 
age 
(years) 
3 5 7 9.41 2 5 11 9.64 0.927 
dosis of 
terbinafine 
mg/kg 4.1 4.3 5.4 9.09 3.2 s.o 8.9 10.14 0.683 
b.w. 
duration of 
treatment 
(weeks) 6.0 12.0 15.0 9.55 8.0 12.0 14.0 9.43 0.964 
acta dennatovenerologica A.P.A. Vol 7, 98, No 3-4 169 
Terbinafine in hair-samples 
Nearly the same concentrations persisted one week 
after the discontinuation of the drug, which demon-
strates that the drug is present in newly grown 
hairs. In some patients very high levels of the drug 
were found. The reason for this might be shaving 
the hair instead of clipping, the later being easier 
to perform in children. In studies performed in 
adult volunteers, the hair was clipped close to the 
skin (10,12). Some of the most superficial cells from 
the stratum corneum were probably present in our 
samples. In tinea capitis it is important to treat not 
only the hair shafts but also the skin between them; 
high levels of the drug in the most superficial parts 
of the skin are necessary for cure. 
The phenomenon of terbinafine exerting its 
therapeutic effect after cessation of therapy has 
already been observed in clinical studies (5,8). In 
some recent studies, even shorter oral terbinafine 
treatments of 1-2 weeks have been successful (7). It 
can be explained by the persistence of high levels 
of the drug in the target tissue. Our observation in 
children was similar. 
More interesting was the finding that the children 
in whom the treatment was not successful had 
lower levels of the drug in hair at the end of 
treatment although there were no differences in 
age, dosage and duration of the treatment compared 
to the group in whom the treatment was successful. 
The reasons for this observation are not known as 
yet. Terbinafine is a highly lipophilic drug; lower 
levels of the drug may be due to lower sebum 
output in those children. M. canis scalp infection is 
one of the most difficult dermatophytosis to treat 
and much higher concentrations of the antifungals 
are probably needed at the site of infection for a 
complete cure. In the future more studies should be 
performed in larger groups of children. The assessment 
of drug levels in the target tissue and its correlation 
with culture analyses may be a useful method of 
evaluating the in vivo effect of systemic treatment 
with antimycotics. 
Acknowledgements: 
The study was performed with kind support of Novartis Pharma 
Services !ne. Slovenia 
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AUTHORS' ADDRESSES 
170 
Vlasta Dragoš MD, dermatologist, Department of Dermatology, University Medica! Centre, 
Zaloška 2, 1552 Ljubljana, Slovenia 
Lijana Zaletel-Kragelj, MD, PhD, Institute of Biomedical Statistics, Medica! Faculty, Vrazov trg 2, 
1000 Ljubljana, Slovenia 
·acta dermatovenerologica A.P.A. Vol 7, 98, No 3-4