Biology Reference
In-Depth Information
initiation has a significant impact on drug clearance. Similarly, significant increases
in sildenafil concentration should be expected when it is used concomitantly with
CYP3A4 inhibitors such as cimetidine and erythromycin (Mukherjee et al.
2009
).
Hypotension was the most commonly observed adverse effect. One infant was
withdrawn from the study because the sildenafil loading infusion (scheduled to be
given over 5 min) had to be stopped after 2 min due to systemic hypotension.
Hypotension was not observed when the loading dose was delivered over 3 h. An
additional infant died due to bilateral tension pneumothoraces, not related to
sildenafil infusion. For the remaining 34 infants, oxygenation improved signifi-
cantly through the course of the sildenafil infusion, with no significant changes in
systemic blood pressure. Only one infant required cannulation for extracorporeal
life support. Of the seven infants enrolled without prior use of iNO, all experienced
a significant improvement in oxygenation within 4 h after sildenafil administration
(Fig.
5
). Only one of the seven infants required iNO, and the other six infants
improved and survived to hospital discharge without requiring either iNO or ECMO
(Steinhorn et al.
2009
). Unlike the previously mentioned studies, sildenafil used in
combination with iNO did not significantly decrease systemic blood pressure or
Fig. 5 Response to sildenafil intravenous infusion without iNO. Seven infants were enrolled
before the need for iNO. Oxygenation index (OI) was improved by 1 h (24.6
4.6 to 16.1
9.9;
*
P ¼
0.0502), with significant and sustained improvement by 4 h after the initiation of sildenafil
(14.7
6.4,
p ¼
0.0088). Of the seven infants who received sildenafil only, the majority (
n ¼
5)
were in cohorts 6-8, meaning that they received the highest maintenance infusion dose of
1.64 mg/kg/day, and differed only in the approach to the loading dose. Of these seven infants,
only one infant required additional treatment with iNO, and that infant was in cohort 4, receiving
loading and maintenance doses that were approximately 20% of the final dose tested in trial.
Reprinted from Steinhorn et al. (
2009
) with permission from Elsevier
