IJT - CIR - February 2024 - 59S

Cherian et al.
59S
Animal
Adenosine. A Draize assay was performed on 3 Japanese
White rabbits according to OECD TG 405.2 The test substance,
100 mg undiluted Adenosine, was instilled into the left
eye of each animal. The eyes, which were not rinsed, were
observed for 21 d. The test substance was considered to be
non-irritating to the eye.
Clinical Studies
Effects of Inhalation
Adenosine. The effect of inhaled Adenosine was studied in
eight asthmatic subjects.45 Before administration of Adenosine,
two baseline blood samples were taken, and five baseline
measurements of specific airway conductance (SGaw) were
made. Volunteers then inhaled a single sample of Adenosine,
ranging from .6 to 6.7 mg/mL. The test material was nebulized
from a volume of 4 mL in disposable nebulizers driven by
compressed air at 8 L/min. Approximately .5 mL of the test
solution left the nebulizer as an aerosol each minute; 12.5% of
this entered the lungs with a mass median particle diameter of
4.5 microns. After inhalation, SGaw and blood sample measurements
were taken at 1, 3, 5, 10, 15, 20, 25, and 30 min.
Significant falls in SGaw from a mean baseline of .124 ± .024
to .046 ± .008 and .066 ± .012 s/cm/water, were observed at 3
and 30 min, respectively. Inhalation did not produce significant
changes in levels of histamine, neutrophil chemotactic
factor, or cyclic adenosine phosphate in the blood.
Adenosine Phosphate and Adenosine Triphosphate. The effects
of aerosolized Adenosine Triphosphate and Adenosine
Phosphate on dyspnea and airway caliber were studied.46 The
perception of dyspnea quantified by a modified Borg Scale of
Perceived Exertion and other symptoms was determined in 10
nonsmokers and 10 patients with asthma. Each subject attended
the laboratory on three occasions. The first visit included
a screening, recording ofmedical history, lung function
assessment, and skin-prick testing of common aeroallergens.
On the second and third visit, subjects were administered
either Adenosine Triphosphate or Adenosine Phosphate, in
aerosolized form. Before, immediately after, and 30 min after
the challenge, spirometry was performed, the Borg score was
determined, and symptoms other than dyspnea were recorded.
In order to determine the Borg scale, subjects were asked to
determine the degree ofbreathlessness they were experiencing
on a scale of 0-10. For the inhalation challenge tests,
Adenosine Triphosphate (.125-512 mg/mL) and Adenosine
Phosphate (.048-400 mg/mL) were dissolved in a normal
saline solution and administered via a breath-activated dosimeter
with an output of 10 μL per inhalation. Participants
wore a nose clip and inhaled 5 breaths of the normal saline
solution, followed by sequential doubling concentrations of
either Adenosine Triphosphate or Adenosine Phosphate.
Subjects who were healthy nonsmokers did experience
dyspnea when given Adenosine Triphosphate or Adenosine
Phosphate. All patients with asthma experienced dyspnea
when given Adenosine Triphosphate, and 90% of patients
with asthma experienced dyspnea when given Adenosine
Phosphate. The geometric mean provocative dose (PD20)in
responsive subjects was 26.9 mg/mL and 39.6 mg/mL for
Adenosine Triphosphate and Adenosine Phosphate, respectively.
In patients with asthma, the perception of dyspnea
assessed by the Borg score increased from .1 to 3.3 and .2 to
2.5 after Adenosine Triphosphate and Adenosine Phosphate,
respectively. Eighty percent of subjects coughed after the
Adenosine Triphosphate challenge, whereas 40% of subjects
coughed after the Adenosine Phosphate challenge. Throat
irritation was noted after the Adenosine Triphosphate and
Adenosine Phosphate challenge in 70% and 35% of subjects,
respectively.
A different study was performed to evaluate whether inhaled
Adenosine Triphosphate or Adenosine Phosphate produces
a tussive response, and whether chronic cough patients
are hypersensitive to these ingredients compared to healthy
volunteers.47 All participants received two cumulative cough
challenges, one with Adenosine Triphosphate and one with
Adenosine Phosphate. Saline (.9%) was used as the solvent for
both Adenosine Phosphate and Adenosine Triphosphate. The
two challenges were administered on two different days, at
least 48 h apart. Each volunteer started with a saline inhalation,
followed by Adenosine Triphosphate or Adenosine Phosphate
delivered in increasing concentrations on a half-log scale from
.1 to 300 mM. The number of coughs produced in the first
15 seconds after inhalation were counted. The challenge was
terminated once the volunteer coughed at least fivetimes (C5),
or the maximum concentration was inhaled. Two out of 19
healthy patients coughed with Adenosine Phosphate, none
reaching C5. Eighteen out of 20 volunteers coughed after
administration of Adenosine Triphosphate, with 15 reaching
C5. Eight out of 20 chronic cough patients coughed with
Adenosine Phosphate, two reaching C5. Eighteen of 19
chronic cough patients reached C5 after inhalation of
Adenosine Triphosphate. The C5 in chronic cough patients
was predominately distributed between 1 mM and 100 mM, as
all patients who reached C5, did so by a concentration of
100 mM.
Adenosine Triphosphate in
Resistance-Trained Athletes
Adenosine Triphosphate. The effect ofAdenosine Triphosphate
in resistance-trained athletes was investigated in a 12-wk, 3phase
randomized, double-blind, and placebo- and dietcontrolled
intervention.48 Phase 1 consisted of a periodized
resistance-training program. Phase 2 was a 2-wk overreaching
cycle in which volume and frequency were increased, followed
by a 2-wk taper (Phase 3). Biochemical parameters

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