Pharmacokinetics of single and multiple oral doses of 5 mg linagliptin in healthy Chinese volunteers
| Autor: | Xiaojin Shi, Christian Friedrich, Peter Zeng, Arne Ring, Hans-Juergen Woerle, Sanjay Patel |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Urinalysis Coefficient of variation Urology Cmax Administration Oral Linagliptin Urine Pharmacokinetics medicine Humans Pharmacology (medical) Adverse effect Pharmacology Dipeptidyl-Peptidase IV Inhibitors medicine.diagnostic_test business.industry Purines Area Under Curve Quinazolines Female Geometric mean business medicine.drug |
| Zdroj: | Int. Journal of Clinical Pharmacology and Therapeutics. 50:889-895 |
| ISSN: | 0946-1965 |
| Popis: | OBJECTIVE To investigate the pharmacokinetic and safety profile of linagliptin after single and multiple doses in healthy Chinese volunteers. METHODS Men and women (n = 12) aged 18 - 45 years with body mass index 19 - 24 kg/m2 received a single 5-mg dose of linagliptin on Day 1, followed by 7-day washout and 6 consecutive days of once-daily administration. Vital signs, electrocardiogram, routine laboratory tests, urinalysis, and adverse events were recorded. Blood and urine analytes were measured by HPLC/MS/MS. RESULTS Linagliptin was rapidly absorbed; median time to maximum concentration was 1.75 h for single dose and 1.5 h at steady-state. Maximum plasma drug concentration (Cmax) after single dose was 4.9 ng/ml (10.4 nM), with a geometric coefficient of variation (gCV) 46%. The corresponding geometric mean area under the plasma concentrationtime curve (AUC) was 71 ng×h ml-1 (150 nmol×h l-1, gCV 25%). At steady-state, Cmax and AUC were 6.7 ng/ml (14.1 nM, gCV 49%) and 96 nmol×h l-1 (204 nmol×h l-1, gCV 25%). An accumulation half-life of ~ 11.5 h (gCV 46.9%) was calculated. Renal excretion of linagliptin was low and < 8% of administered dose at steady-state (< 2% at Day 1). Single and multiple daily oral doses of 5 mg linagliptin were safe and well tolerated. No adverse events or clinically significant changes in laboratory tests, vital signs, or physical examination were reported. CONCLUSIONS Linagliptin demonstrated a favorable safety profile in healthy Chinese volunteers, with a pharmacokinetic profile that was similar to that observed previously in subjects of Japanese, Caucasian, or African American origin. |
| Databáze: | OpenAIRE |
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