Biology Reference
In-Depth Information
Rolipram is rapidly absorbed after an oral administration. Absolute bioavailability
was 73% (hepatic first-pass effect) (Krause et al.
1989
). The maximum plasma
concentration is reached after 15-45 min (Table
1
).
The observed volume of distribution was small (0.45 l
1
kg), indicating lack of
distribution to deep compartments.
Rolipram is extensively metabolized (Krause and K
uhne
1993
). The half-life
of rolipram is short with approximately 3 h and the drug had to be administered
three times a day (Krause et al.
1989
) to achieve what was assumed being the
therapeutically desired exposure. Rolipram is eliminated mainly by renal excretion
(Krause et al.
1990
). No pharmacokinetic differences have been observed between
both enantiomers of rolipram (Krause et al.
1990
).
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Table 1 Pharmacokinetic parameters of PDE4 inhibitors in healthy adults following a single oral
dose
Substance
Dose (mg)
p.o.
T
max
(h)
C
max
(ng/ml)
t
1/2
(h)
AUC
0-inf
(ng h ml
1
)
Reference
Rolipram
a
1
0.4
34
3
250
Krause et al. (
1989
)
Ibudilast
b
10
4
25
12
>
334
Uchida et al.
(
1985
); labeling
information
KETAS
®
Capsules 10 mg
Tetomilast
50
2.75
5.7
24
140
Mallikaarjun et al.
(
2006
)
Cilomilast
10
3
823
7
7,160
Zussman et al.
(
2001a
)
Roflumilast
0.5
1
7.7
22.8
51
Lahu et al. (
2010
)
(Roflumilast
N-oxide
c
)
N/A
4
10.9
24.7
529
Lahu et al. (
2011
)
a
racemic drug
b
Asian males; sustained release formulation
c
active metabolite; p.o. oral
4.2
Ibudilast
Ibudilast is well absorbed after oral administration. Oral exposures adjusted for
administered dose are higher in rats and humans than other species (Rolan et al.
2009
). The maximum plasma concentration (
C
max
) in humans is reached after 4-6 h
(Rolan et al.
2008
).
The plasma protein binding of ibudilast is high across species (Sanftner et al.
2009
). Ibudilast exhibits rapid, extensive, and reversible CNS partitioning (Sanftner
et al.
2009
).
Ibudilast is metabolized by numerous cytochrome P450 isozymes and it is not
predicted to be a clinically relevant inhibitor or inducer of CYP enzymes in vivo
(Rolan et al.
2009
).
