Biology Reference
In-Depth Information
Table 5.1
Pharmacokinetic studies of kisspeptin in humans
Route of
administration
Isoform
Assay
Results
References
Kisspeptin-10
Intravenous bolus
(men, women)
RIA, sheep
polyclonal
IR peaked at fi rst time point
(15 min), undetectable
by 30 min
[
14
]
Intravenous
infusion (men,
women)
RIA, sheep
polyclonal
IR peaked 30 min after
infusion started; IR
half-life 4 min after
infusion stopped
[
14
]
Subcutaneous
bolus (women)
RIA, sheep
polyclonal
IR peaked at fi rst time point
(15 min), then gradually
declined to baseline over
45-120 min, half-life
~20 min
[
14
]
In vitro (plasma)
Mass spectrometry
Half-life 55 s
[
11
]
Kisspeptin-54
Intravenous
infusion (men)
RIA, sheep
polyclonal
IR peaked 30 min after
infusion started; IR
half-life 28 min after
infusion stopped
[
13
]
Intravenous bolus
(women)
RIA, sheep
polyclonal
Gradual increase in IR,
peaking 40 min after
bolus and still measur-
able by the end of the 3-h
study
[
14
]
Subcutaneous
bolus (women)
RIA, sheep
polyclonal
IR peaked at fi rst time point
(15 min after bolus); at
low doses IR disap-
peared by 3.5 h, at high
doses IR essentially
undiminished by the end
of the 4-h study
[
15
]
IR
immunoreactivity;
RIA
radioimmunoassay
Challenges in Determining the Pharmacokinetics of Kisspeptin
A key component of a pharmacokinetic study is an accurate assay for measuring the
concentration of a drug. Ideally, the assay can distinguish the drug and its active
metabolites from inactive breakdown products. Two methods have been used to
measure kisspeptin: immunoassays and mass spectrometry.
Immunoassays use antibodies that recognize specifi c epitopes on the target mole-
cule. Assays based on monoclonal antibodies recognize a single epitope; if this epit-
ope is destroyed through proteolysis or altered through some other form of
modifi cation, the resulting metabolite cannot be detected by the assay, regardless of
whether the metabolite is biologically active or inactive. Assays based on polyclonal
antibodies recognize multiple epitopes and are therefore less susceptible to having
molecules rendered “invisible” by the loss of a single epitope. However, assays based
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