Assessment of the pharmacokinetic interaction between the novel DPP-4 inhibitor linagliptin and a sulfonylurea, glyburide, in healthy subjects.
Drug Metab Pharmacokinet
; 26(2): 123-9, 2011.
Article
en En
| MEDLINE
| ID: mdl-21084763
ABSTRACT
The aim of this study was to investigate the effect of the dipeptidyl peptidase-4 inhibitor linagliptin on the pharmacokinetics of glyburide (a CYP2C9 and CYP3A4 substrate) and vice versa. This randomized, open-label, three-period, two-way crossover study examined the effects of co-administration of multiple oral doses of linagliptin (5 mg/day × 6 days) and single doses of glyburide (1.75 mg/day × 1 day) on the relative bioavailability of either compound in healthy subjects (n = 20, age 18-55 years). Coadministration of glyburide did not alter the steady-state pharmacokinetics of linagliptin. Geometric mean ratios (GMRs) [90% CI] for (linagliptin + glyburide)/linagliptin AUC(τ,ss) and C(max,ss) were 101.7% [97.7-105.8%] and 100.8% [89.0-114.3%], respectively. For glyburide, there was a slight reduction in exposure of â¼14% when coadministered with linagliptin (GMRs [90% CI] for (glyburide + linagliptin)/glyburide AUC(0-∞) and C(max) were 85.7% [79.8-92.1%] and 86.2% [79.6-93.3%], respectively). However, this was not seen as clinically relevant due to the absence of a reliable dose-response relationship and the known large pharmacokinetic interindividual variability of glyburide. These results further support the assumption that linagliptin is not a clinically relevant inhibitor of CYP2C9 or CYP3A4 in vivo. Coadministration of linagliptin and glyburide had no clinically relevant effect on the pharmacokinetics of linagliptin or glyburide. Both agents were well tolerated and can be administered together without the need for dosage adjustments.
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Bases de datos:
MEDLINE
Asunto principal:
Purinas
/
Quinazolinas
/
Compuestos de Sulfonilurea
/
Gliburida
/
Inhibidores de la Dipeptidil-Peptidasa IV
/
Hipoglucemiantes
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Drug Metab Pharmacokinet
Asunto de la revista:
FARMACOLOGIA
/
METABOLISMO
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania