Das pharmakologische Profil von Sildenafil zeigt neben der PDE5-Inhibition auch eine geringe Aktivität an der PDE6 in der Retina. Dies erklärt visuelle Nebenwirkungen wie Farbsehstörungen, die gelegentlich auftreten. Die orale Bioverfügbarkeit beträgt etwa 40 %, mit einer hohen Bindung an Plasmaproteine. Das Verteilungsvolumen ist groß, sodass die Substanz rasch in verschiedene Gewebe gelangt. Die Metabolisierung erfolgt hepatisch und produziert einen aktiven Metaboliten, der die pharmakologische Wirkung ergänzt. Nebenwirkungen sind dosisabhängig und umfassen Kopfschmerzen, Hautrötung und Dyspepsie. Bei Vergleichen innerhalb der Wirkstoffklasse wird viagra original regelmäßig als Beispiel für eine Substanz mit schneller, aber kurzzeitiger Wirkung aufgeführt.

Microsoft word - effect of modafinil on the pharmacokinetics of ethinyl estr

Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy
volunteers.
Clin Pharmacol Ther 2002 Jan;71(1):46-56 (ISSN: 0009-9236)
Robertson P; Hellriegel ET; Arora S; Nelson M
Department of Drug Disposition, Cephalon, Inc., West Chester, PA 19380, USA.
[email protected].
BACKGROUND: Modafinil has been reported to produce a concentration-related induction of
CYP3A4/5 activity in vitro in primary cultures of human hepatocytes. OBJECTIVE: Our
objective was to determine whether the pharmacokinetics of steady-state ethinyl estradiol (INN,
ethinylestradiol) and single-dose triazolam were altered after 4 weeks of modafinil treatment
in volunteers. METHODS: This was a placebo-controlled, single-blind, single-period study in
41 female subjects who were receiving long-term treatment with an oral contraceptive that
contained ethinyl estradiol (0.035 mg) and norgestimate (0.180-0.250 mg). Pharmacokinetic
profiles for ethinyl estradiol and for a single oral dose of triazolam (0.125 mg) were obtained
the day before initiation of treatment with modafinil (200 mg for 7 days, followed by 400 mg for
21 days) or placebo (28 days). A second dose of triazolam was administered with the final
dose of modafinil, and pharmacokinetic profiling was repeated. RESULTS: The modafinil
treatment group had a marked decrease in maximum observed plasma concentrations and
areas under the plasma concentration-time curve for triazolam relative to placebo, with a much
smaller decrease in these parameters for ethinyl estradiol. The half-life of triazolam was also
decreased, but the half-life of ethinyl estradiol did not appear to be affected by treatment with
modafinil. CONCLUSION: Modafinil induced CYP3A4/5 activity in humans in vivo, suggesting
that there is potential for metabolic drug-drug interactions between modafinil and substrates of
CYP3A4/5. However, the induction appeared to be more gastrointestinal than hepatic in nature.
Therefore significant metabolic drug-drug interactions are most likely to occur with compounds
(such as triazolam) that undergo significant gastrointestinal CYP3A4/5-mediated first-pass
metabolism.
CAS Registry / EC
Major Subject Heading(s)
Minor Subject Heading(s)
 Chromatography, High
 28911-01-5 (Triazolam)
 Triazolam
 Half-Life
 Human
protein, human)
 Mixed Function Oxygenases  EC 1.14.14.1 (nifedipine [metabolism]  Sedatives, Nonbarbiturate [adverse effects]  Single-Blind Method
 Spectrophotometry,
Ultraviolet
 Spectrum Analysis, Mass
 Triazolam [adverse effects]

Source: http://www.docseducation.com/sites/default/files/Effect_of_modafinil_on_the_pharmacokinetics_of_ethinyl.pdf