High inter-individual variability of vardenafil pharmacokinetics in patients with pulmonary hypertension.
Eur J Clin Pharmacol
; 69(2): 197-207, 2013 Feb.
Article
en En
| MEDLINE
| ID: mdl-22732766
ABSTRACT
PURPOSE:
To evaluate the pharmacokinetic parameters of a single oral dose of vardenafil in patients with pulmonary hypertension (PH).METHODS:
Sixteen patients with PH received vardenafil in single oral doses (20, 10 or 5 mg), and repeated blood sampling for up to 9 h was performed. Vardenafil plasma concentration was determined using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were calculated using model-independent analysis.RESULTS:
The plasma vardenafil concentration increased rapidly and exhibited a median time to maximum plasma concentration (t(max)) of 1 h and a mean elimination half-life (t(1/2)) of 3.4 h. The geometric mean and standard deviation of (1) the peak plasma concentration (C(max)) was 21.4 ± 1.7 µg/L, (2) the normalized C(max) (C(max, norm)) 79.1 ± 1.6 g/L, (3) the area under the time-concentration curve (AUC) 71.5 ± 1.6 µg · h/L and (4) the normalized AUC (AUC(norm)) 261.6 ± 1.7 g · h/L. Patients co-medicated with bosentan reached t(max) later and had a 90% reduction of C(max), C(max, norm), AUC and AUC(norm).CONCLUSION:
The pharmacokinetic profile of vardenafil overall revealed considerable inter-individual variability in patients with PH. Co-medication with bosentan resulted in a pharmacokinetic drug interaction, leading to significantly decreased plasma concentrations of vardenafil. Therapeutic drug monitoring for individual dose optimization may be warranted.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Piperazinas
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Vasodilatadores
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Inhibidores de Fosfodiesterasa 5
/
Hipertensión Pulmonar
/
Imidazoles
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Aged
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Aged80
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Eur J Clin Pharmacol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Suecia