Table 1.

Pharmacokinetic parameters of DA-1131

Treatment groupPharmacokinetic parametera
Terminal t1/2 (min)AUC0–∞ (μg · min/ml)AUMC0–∞ (μg · min2/ml)MRT (min)CL (ml/min/kg)CLR (ml/min/kg)CLRN(ml/min/kg)Vss(ml/kg)Xug (% of i.v. dose)
Ratsb
 Treatment I15.2 ± 3.1513,900 ± 2,480167,000 ± 43,30012.0 ± 2.0814.3 ± 2.796.07 ± 1.608.01 ± 1.64167 ± 51.543.8 ± 6.06
 Treatment II27.6 ± 2.94d 18,300 ± 1,930d 381,000 ± 94,700d 20.8 ± 4.14d 10.9 ± 1.20f 7.19 ± 1.343.00 ± 1.92d 221 ± 44.7e 68.2 ± 13.7d
Rabbitsc
 Treatment III19.1 ± 6.953,880 ± 1,24042,700 ± 23,00010.8 ± 3.1612.9 ± 5.176.34 ± 2.776.77 ± 3.78128 ± 59.245.4 ± 12.4
 Treatment IV15.9 ± 3.0910,100 ± 1,160d 141,000 ± 31,400d 13.9 ± 2.08e 4.96 ± 0.567d 2.11 ± 0.574d 2.41 ± 0.970f 68.1 ± 10.9f 47.5 ± 14.5
Dogsc
 Treatment V47.2 ± 5.707,680 ± 1,170338,000 ± 74,40043.8 ± 3.886.51 ± 0.9453.78 ±0.4922.61 ± 0.780285 ± 35.358.3 ± 7.35
 Treatment VI48.2 ± 3.759,320 ± 817e 465,000 ± 58,700d 49.8 ± 3.96f 5.37 ± 0.508e 2.60 ± 1.002.28 ± 0.783266 ± 28.654.8 ± 15.1
  • a Values are means ± standard deviations.

  • b Rats were given a 1-min intravenous infusion of DA-1131 (200 mg/kg) without (treatment I) or with (treatment II) cilastatin (200 mg/kg).

  • c Rabbits and dogs were given a 1-min intravenous infusion of DA-1131 (50 mg/kg) without (treatments III and V, respectively) or with (treatments IV and VI, respectively) cilastatin (50 mg/kg).

  • d P < 0.001.

  • e P < 0.05.

  • f P < 0.01.

  • g Xu , drug amount in urine.