Pharmacokinetic Study of Saxagliptin in Healthy Chinese Subjects
Clinical Drug Investigation, 06/12/2012
Li H et al. – Saxagliptin 5 mg (single dose and once–daily doses for 5 days) was generally well tolerated; the pharmacokinetics of saxagliptin and 5–hydroxy saxagliptin in healthy Chinese subjects were consistent with previous assessments in the saxagliptin clinical development program.Methods
- This was an open–label, 9–day study conducted at the Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
- Sixteen healthy Chinese subjects of both sexes between 21 and 33 years of age were administered saxagliptin 5 mg orally on day 1, then once daily on days 3–7.
- Pharmacokinetic variables for saxagliptin (primary outcome) and its active metabolite, 5–hydroxy saxagliptin (secondary outcome), after single and multiple oral doses of saxagliptin were assessed.
- Safety was also assessed.
- Saxagliptin was absorbed rapidly (median time to reach maximum concentration [tmax]: 0.5 and 1 hour on days 1 and 7, respectively), and its pharmacologically active metabolite, 5–hydroxy saxagliptin, appeared in plasma (median tmax: 1.0 and 1.5 hours, respectively).
- Plasma exposure to 5–hydroxy saxagliptin was approximately 2– to 3–fold higher than exposure to saxagliptin.
- Plasma concentration–time profiles for saxagliptin and 5–hydroxy saxagliptin were similar on days 1 and 7, with no evidence of drug accumulation on repeated dosing.
- The elimination half–lives (t½) for saxagliptin and 5–hydroxy saxagliptin were approximately 3 and 4 hours, respectively, with renal excretion as the primary route of elimination.
- After single and multiple dosing, 54.48% and 52.60%, respectively, of the administered saxagliptin dose was recovered in urine as unchanged drug or 5–hydroxy saxagliptin.
- Saxagliptin was generally well tolerated.
- Six (37.5%) subjects experienced an adverse event (AE).
- All AEs were mild in intensity and judged by the investigator as not related to the study medication.
- There were no deaths, serious AEs, discontinuations due to AEs, or other clinically significant AEs during this study.