Table 1 Pharmacokinetic parameters of Alteplase and mt-PA after the intravenous administration of 100, 200 and 400 IU mt-PA and 4000 IU Alteplase to rats.

From: Scale up and pharmacokinetic study of a novel mutated chimeric tissue plasminogen activator (mt-PA) in rats

Parameters

Alteplase (n = 6)

Mt-PA (n = 13)

4000 IU

100 IU

200 IU

400 IU

t1/2 (α) (min)

1.8 ± 0.03

1.85 ± 0.05

1.82 ± 0.02

1.83 ± 0.02

t1/2 (β) (min)

8.3 ± 1.3

20.3 ± 1.4

19.1 ± 3.8

26.1 ± 3.4

K10 (min−1)

0.3 ± 0.03

0.11 ± 0.03

0.08 ± 0.02

0.09 ± 0.03

K12 (min−1)

0.07 ± 0.02

0.18 ± 0.01

0.16 ± 0.01

0.19 ± 0.02

K21 (min−1)

0.12 ± 0.01

0.12 ± 0.03

0.18 ± 0.01

0.12 ± 0.03

AUC 0→∞ (IU.min/mL)

28.3 ± 3.3

17 ± 1.6

59.2 ± 23.9

83.3 ± 30.8

AUMC (min.min.IU/mL)

173.6 ± 63.9

398.2 ± 78.2

1608.0 ± 940.3

2749.4 ± 1301.0

Vss (mL)

838.0 ± 117.6

137.6 ± 5.2

91.2 ± 17.7

163.9 ± 39.9

V1 (mL)

509.3 ± 13.7

54.6 ± 7.2

48.3 ± 8.4

58.7 ± 4.5

V2 (mL)

328.7 ± 111.8

82.9 ± 9.2

42.9 ± 9.3

105.2 ± 36.7

CLp (mL/min)

142.6 ± 15.2

5.9 ± 0.6

3.9 ± 1.6

5.4 ± 2.1

MRT (min)

6 ± 1.5

23.3 ± 2.5

25.4 ± 5.7

31.8 ± 6.1

  1. Abbreviations: t1/2 (α), the distribution half-life; t1/2 (β), the elimination half-life; K10, the first-order elimination rate constant; k12 and k21, the elimination rate constants between the central and the peripheral compartments; AUC0→∞, the Area Under the plasma concentration-time Curve; AUMC, the area under the first moment curve; Vss, the volumes of distribution at steady state; V1, the distribution volume of the central compartment; V2, the distribution volumes of the peripheral compartment; CLp, the plasma clearance; MRT, the mean residence time. Each parameter was presented as Mean ± SD; n = 3–6/dose.
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