TABLE 1

Tissue (+)-METH and (+)-AMP pharmacokinetic parameters in control and anti-(+)-METH mAb-treated rats a


Tissue

Drug

AUC04.5 h

AUCtissue/AUCserum
Control b
Anti-(+)-METH mAb c
Control b
Anti-(+)-METH mAb c
ng · h/ml or ng · h/g
Serum METH 234 ± 10 16,282 ± 282 *
AMP 71 ± 2 82 ± 3
Brain METH 2235 ± 58 907 ± 30 * 9.1 0.05 d (3.6) e
AMP 661 ± 22 280 ± 8 * 8.5 3.4
Liver METH 1325 ± 133 2110 ± 42 * 5.2 0.13 (8.8)
AMP 467 ± 44 194 ± 14 * 5.9 2.4
Testis METH 1837 ± 126 2101 ± 184 7.4 0.13 (8.7)
AMP 456 ± 155 193 ± 30 * 5.9 3.1
Kidney METH 8606 ± 279 4944 ± 255 * 34.2 0.31 (20.9)
AMP 2126 ± 100 1274 ± 116 * 30.7 15.5
Spleen METH 2956 ± 186 2407 ± 280 11.9 0.15 (10.0)

AMP
911 ± 80
473 ± 34 *
11.8
4.9
  • * Significant differences from control values (p <0.05).

  • a Values (± S.E.) were calculated using Bailer's method.

  • b Control rats were treated with vehicle 17 h before (+)-METH (1 mg/kg).

  • c Rats were treated with anti-(+)-METH mAb6H4 17 h before (+)-METH (1 mg/kg).

  • d Values were calculated using total (+)-METH serum AUC04.5 h from mAb-treated rats. For control rats, serum protein binding is negligible; thus, total AUC ≈ free AUC.

  • e Values were calculated using free (+)-METH serum AUC04.5 h from mAb-treated rats.