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
Leucovorin Pharmacology, Pharmacokinetics, Studies, Metabolism - Leucovorin
Leucovorin Pharmacology, Pharmacokinetics, Studies, Metabolism - Leucovorin
CLINICAL PHARMACOLOGY
Leucovorin is a mixture
of the diastereoisomers of the 5formyl derivative of tetrahydrofolic
acid. The biologically active component
of the mixture is the
()Lisomer, known as Citrovorum
factor, or ()folinic acid. Leucovorin does not require
reduction by the enzyme
dihydrofolate reductase
in order to participate
in reactions utilizing folates as a source
of "onecarbon" moieties. Following oral
administration, leucovorin is rapidly absorbed and enters the general
body p.o.
of reduced folates.
The increase in plasma
and serum reduced folate
activity (determined
microbiologically with Lactobacillus casei ) seen after oral
administration of leucovorin is predominantly due to 5methyltetrahydrofolate.
Following a 20 mg dose
of leucovorin calcium,
the mean maximum
serum total reduced folate concentrations were:
| Tablet |
364 ± 12.1 ng/mL at |
2.0 ± 0.07 hours |
| Oral Solution |
375 ± 12.8 ng/mL at |
2.1 ± 0.11 hours |
| Parenteral |
355 ± 17.2 ng/mL at |
0.96 ± 0.10 hours |
The half-life of plasma
5-formyltetrahydrofolate was 1.5±0.08 hours and that of the
5-methyltetrahydrofolate was 3.0±0.09 hours.
Oral tablets produced equivalent
bioavailability
(8% difference) when compared to the parenteral
administration. The parenteral
solution also provided
equal bioavailability
to the tablets when administered orally (2% difference). Oral absorption
of leucovorin is saturable at doses above 25 mg. The apparent
bioavailability
of leucovorin was 97% for 25 mg, 75% for 50 mg
and 37% for 100 mg.
top
