A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Candin Pharmacology, Pharmacokinetics, Studies, Metabolism - Candida Albicans
Candin Pharmacology, Pharmacokinetics, Studies, Metabolism - Candida Albicans
CLINICAL PHARMACOLOGY
Cellular or delayed-type hypersensitivity (DTH) can be assessed by intracutaneous
testing with bacterial, viral and fungal antigens to which most healthy
persons are sensitized. A positive skin test denotes prior antigenic exposure,
T-cell competency and an intact inflammatory response (1,2). The reaction
usually peaks 48 hours after antigen is introduced into the skin and is
manifest as induration at the test site.
Recall antigens may be useful in evaluating delayed-type hypersensitivity
by eliciting positive induration reactions 48 to 72 hours after intracutaneous
administration. Except for mumps skin test antigen, most commonly used
recall antigens were developed for other purposes, and the size of the
reaction elicited may not be directly related to cellular immunity because
of variability in antigen source and dose and skin test administration
and measurement techniques. Useful antigens are those which elicit a reaction
size ³5
mm in more than 50% of normal individuals. The combination of results
from skin testing with more than one antigen should result in detection
of DTH in at least 95% of normal subjects (2).
The inflammatory response associated with the DTH reaction is characterized
by an infiltration of lymphocytes and macrophages at the site of antigen
deposition. Specific cell types that appear to play a major role in the
DTH response include CD4+ and CD8+ T lymphocytes
which leave the recirculating lymphocyte pool in response to exogenous
antigen (3). Both CD4+ and CD8+ lymphocytes have
been recovered from DTH reactions elicited by Candida antigen (4).
In the literature, the incidence of DTH reactions to unstandardized Candida
antigens has been reported to vary from 52 - 89%, depending upon the strength
of the antigen and the mm induration required for a positive test (5,6,7,8,9).
Published studies have reported that antigens of Candida albicans are
useful in the assessment of diminished cellular immunity in persons infected
with human immunodeficiency virus (10,11). Responses to DTH antigens have
been reported to have prognostic value in patients with cancer (5).
RESPONSE TO CANDIN® in Healthy Adults (Table1): In
one group of 18 subjects, 14 (78%) of the individuals reacted to CANDIN®
with an induration response of ³5
mm at 48 hours. In a second study of 35 subjects, 21 (60%) had induration
reactions ³5
mm at 48 hours. In this study, 65% of males tested positive compared to
53% of females; the mean induration in responding males was 12.8 mm and
in responding females was 13.0 mm. When subjects in these studies were
tested with two reagents, CANDIN® and Mumps Skin Test Antigen,
92% were positive to at least one antigen, a higher response rate than
to either antigen used alone (15).
RESPONSE TO CANDIN® in Adults with HIV Infection:
In one study (Table 2). the skin test responses of adults with HIV infection
were compared to those of healthy control subjects (age range AIDS 22-65,
HIV positive 20 - 45, Controls 25 - 69). When HIV infected subjects were
classified by the CDC’s 1993 revised classification system for H.I.V infection
(12), a significant difference was found between AIDS patients and normal
controls in both mean induration (p = 0.01) and proportion with ³5
mm response (p< 0.01). The responses in HIV-infected patients (without
AIDS-indicating conditions or AIDS-indicating CD4 T-cell counts)
were less than in normal subjects, but the differences were not statistically
significant.
In a second study involving 20 male patients (age range 26 - 57) diagnosed
with AIDS based on clinical criteria only, one subject responded to CANDIN®.
In the same study 65% of the male control subjects had DTH reactions 5
mm to CANDIN® (Table 1, Study 2). The mean induration response
at 48 hours for control subjects was 8.33 mm compared to 1.78 mm for the
AIDS subject. AIDS vs. control p-values were < 0.01 mean induration
and <0.01 induration 5 mm.
Because HIV infection can modify the DTH response to tuberculin, it is
advisable to skin test HIV-infected patients at high risk of tuberculosis
with antigens in addition to tuberculin (16). In a published study of
DTH anergy, 479 subjects (334 males and 145 females) infected with HIV
and being screened for tuberculosis were skin tested with several additional
antigens, including CANDIN® supplied under IND to the investigators.
Only 12% reacted to tuberculin (³5
mm), 57% reacted to CANDIN® (³3
mm) and 60% reacted to either tuberculin or CANDIN® or
both. In this study, a 3 mm induration response to CANDIN®
was considered positive. The authors concluded that in HIV-infected subjects,
testing with other DTH antigens increases the accuracy of interpretation
of negative tuberculin reactions.
In one study of 18 patients with lung cancer, CANDIN®
elicited a positive induration response in five patients (28%). In a second
series of 20 patients with metastatic cancer, no reactions ³5
mm were observed (Table 3).
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