Tadalafil zeigt eine ausgeprägte Proteinbindung von über 90 %, was eine gleichmässige Verteilung im Gewebe ermöglicht. Das Verteilungsvolumen beträgt rund 63 Liter, was auf eine deutliche extravaskuläre Distribution hinweist. Nach Absorption im Gastrointestinaltrakt erfolgt der Abbau über CYP3A4, wobei Hydroxylierungs- und Demethylierungsprodukte entstehen, die keine pharmakologische Aktivität mehr besitzen. Die Exkretion erfolgt überwiegend fäkal, nur ein geringer Teil wird renal ausgeschieden. Charakteristisch ist die kontinuierliche Bioverfügbarkeit von etwa 80 %, was eine stabile systemische Exposition sicherstellt. Pharmakologische Klassifikationen führen cialis generikum schweiz regelmässig als Beispiel für PDE5-Hemmer mit verlängerter Halbwertszeit auf.

No slide title

Similar 96-week Renal Safety Profile of
Tenofovir Disoproxil Fumarate (TDF) versus
Stavudine (d4T) when used in Combination
with Lamivudine (3TC) and Efavirenz (EFV) in
Antiretroviral Naïve Patients
JE Gallant1, AL Pozniak2, S Staszewski3, B Lu4, J Sayre4 and
A Cheng4 for the Study 903 Team
1Johns Hopkins Univ School of Medicine, Baltimore, MD, USA; 2 Chelsea and Westminster
Hosp, London, UK; 3University Hospital, J.W. Goethe-Universität, Frankfurt, Germany;
4Gilead Sciences, Foster City, CA, USA.
43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy
September 14-17, 2003
Chicago, Illinois
Poster No. H- 840
Background
Study 903 is an ongoing 144 week, randomized,double-blind, international multicenter trial whichcompares TDF and d4T when used in combinationwith EFV and 3TC in antiretroviral treatment naïvepatients.
Case reports of renal dysfunction have recentlybeen published1-6 Main Inclusion Criteria
• HIV-1 infected patients naïve to antiretroviral treatment• 18 - 65 years of age• Plasma HIV RNA > 5,000 copies/mL• No significant laboratory or clinical abnormalities• No CD4+ cell count criteria• Serum Creatinine < 1.5 mg/dL• Serum Phosphorus ≥ 2.2 mg/dL• Calculated Creatinine Clearance ≥ 60 mL/min Study Design: Randomization
ART-naive
d4T placebo BID
patients
Stratification by:
• plasma HIV RNA >/< 100,000 c/ml
• CD4 count >/< 200 cells/mm³
randomized
TDF placebo QD
Baseline Characteristics
TDF + 3TC + EFV
d4T + 3TC + EFV
Serum Creatinine
Maximum Toxicity Grade
TDF + 3TC + EFV
d4T + 3TC + EFV
0-96 Weeks in mg/dL
Consecutive Visits with Graded Creatinine
TDF+3TC+EFV
d4T+3TC+EFV
Pat
of
er
b
m
Consecutive Visits
Serum Phosphorus
Maximum Toxicity Grade
TDF + 3TC + EFV
d4T + 3TC + EFV
0-96 Weeks in mg/dL
Consecutive Visits with Graded Serum
Phosphorus
TDF+3TC+EFV
d4T+3TC+EFV
tien
a
f P 10
Consecutive Visits
Proteinuria
Maximum Toxicity Grade
TDF + 3TC + EFV
d4T + 3TC + EFV
0-96 Weeks in mg/dL
Glucosuria
Maximum Toxicity Grade
TDF + 3TC + EFV
d4T + 3TC + EFV
0-96 Weeks in mg/dL
Mean Increase from Baseline in Calculated
Creatinine Clearance (Calc Cr Cl)
TDF + 3TC + EFV
d4T + 3TC + EFV
Summary of Results: Parameters through
96 weeks
Parameters through 96 weeks
TDF+3TC+EFV
d4T+3TC+EFV
Mean Change from Baseline inCalc Cr Cl* (mL/min) Conclusions
• The renal safety profile was similar between the
patients receiving tenofovir DF or stavudine plus
lamivudine and efavirenz through 96 weeks
• No patients discontinued study due to tenofovir
DF-related renal abnormalities
• No patient developed Fanconi’s Syndrome
through 96 weeks
References
1Blick G, et al. 10th CROI, Boston, MA, February 10-14, 2003. Poster 718 2Reynes J, et al. 10th CROI, Boston, MA, February 10-14, 2003. Poster 717 5Murphy MD, et al. CID 2003; 36:1082-1085 6Shere-Wolfe KD, et al. CID 2002; 35:1137

Source: http://www.thebody.org/confs/icaac2003/pdfs/H-840_slides.pdf