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
Thioplex Pharmacology, Pharmacokinetics, Studies, Metabolism - Thiotepa (injection)
Thioplex Pharmacology, Pharmacokinetics, Studies, Metabolism - Thiotepa (injection)
CLINICAL PHARMACOLOGY
Thiotepa is a cytotoxic
agent of the polyfunctional
type, related chemically and pharmacologically to nitrogen
mustard. The radiomimetic
action of thiotepa is
believed to occur through the release
of ethylenimine radicals which, like irradiation, disrupt the bonds
of DNA. One of the principal
bond disruptions is initiated
by alkylation of
guanine at the N?7 position,
which severs the linkage
between the p.r.n. base
and the sugar and liberates
alkylated guanines.
The pharmacokinetics
of thiotepa and TEPA
in thirteen female patients
(45 - 84 years) with advanced stage
ovarian cancer
receiving 60 mg and 80 mg
thiotepa by intravenous
infusion on subsequent
courses given at 4-week intervals are presented in the following
table:
|
Pharmacokinetic
Parameters
(units)
|
Mean ± SEM |
| Thiotepa |
TEPA |
| 60 mg |
80 mg |
60 mg |
80 mg |
| Peak Serum concentration
(ng/mL) |
1331 ± 119 |
1828 ± 135 |
273 ± 46 |
353 ± 46 |
| Elimination half-life
(h) |
2.4 ± 0.3 |
2.3 ± 0.3 |
17.6 ± 3.6 |
15.7 ± 2.7 |
| Area under the curve
(ng/h/mL) |
2832 ± 412 |
4127 ± 668 |
4789 ± 1022 |
7452 ± 1667 |
| Total body clearance
(mL/min) |
446 ± 63 |
419 ± 56 |
|
|
TEPA, which possesses cytotoxic
activity, appears to be the major metabolite of thiotepa
found in human serum
and urine. Urinary excretion
of 14C-labeled thiotepa and metabolites
in a 34-year old patient
with metastatic carcinoma of the cecum
who received a dose of
0.3 mg/kg intravenously was 63%. Thiotepa and TEPA in urine
each accounts for less than 2% of the administered dose.
The pharmacokinetics
of thiotepa in renal
and hepatic dysfunction
patients have not been evaluated. Possible pharmacokinetic interactions
of thiotepa with any concomitantly administered medications have
not been formally investigated.
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