Comparison of pharmacokinetics of NS-105, a novel agent for cerebrovascular disease, in elderly and young subjects

Int J Clin Pharmacol Res. 1999;19(1):1-8.

Abstract

Pharmacokinetics of NS-105, a novel agent for cerebrovascular disease, in elderly subjects were compared with those in younger subjects. Fourteen healthy male volunteers (7 elderly subjects aged 68-79 years and 7 young subjects aged 20-32 years) were included in the study. In a parallel group design, a tablet containing 100 mg NS-105 was administered orally after breakfast. One young subject was excluded from the pharmacokinetic analyses owing to an insufficient urine collection. The maximum plasma concentration (Cmax) was higher in the elderly (3.06 +/- 0.69 vs. 2.13 +/- 0.34 micrograms/ml, the elderly vs. the young, mean +/- SD, p = 0.0117) and area under the plasma concentration curve (AUC) was also higher in the elderly (24.6 +/- 4.4 vs. 14.4 +/- 3.1 micrograms.hr/ml, p = 0.0006). There is a tendency that time to reach Cmax was longer in the elderly (2.1 +/- 1.1 vs. 1.3 +/- 0.5 hr, p = 0.1199), and a tendency of prolongation of elimination half-life. Urinary recovery of NS-105 was less in the elderly up to 8 h after administration, while total recovery of the dose was not different in the two groups. Total clearance was reduced in the elderly (0.076 +/- 0.013 vs. 0.121 +/- 0.025l/kg/hr, p = 0.0013) and the decrease seemed to be mainly due to a decrement in renal clearance of the drug in the elderly. A significant correlation was found between renal clearance of NS-105 and creatinine clearance of each subject (r = 0.583, p = 0.0364). These observations indicate that the plasma concentration of NS-105 will increase in elderly subjects mainly due to a decrement in renal clearance of the drug. Careful observation is needed when prescribing the drug to an elderly patient.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Analysis of Variance
  • Area Under Curve
  • Cerebrovascular Disorders
  • Chromatography, High Pressure Liquid
  • Humans
  • Kidney / physiology
  • Least-Squares Analysis
  • Linear Models
  • Male
  • Metabolic Clearance Rate / physiology
  • Nootropic Agents / blood
  • Nootropic Agents / pharmacokinetics*
  • Nootropic Agents / urine
  • Piperidines / blood
  • Piperidines / pharmacokinetics*
  • Piperidines / urine
  • Proline / analogs & derivatives*
  • Proline / blood
  • Proline / pharmacokinetics
  • Proline / urine

Substances

  • 5-oxo-D-prolinepiperidinamide monohydrate
  • Nootropic Agents
  • Piperidines
  • Proline