1 y ml / h kg x mg /d y 2. 5 ml / h kg 0. 3 ml / h kg y = 0. 143 + 0. 046 x r = 0. 994 7 10 PAVELKA 2 Wistar 5 Br - Cl - HCO3 - ClO - 4 SCN - 14 d 82

1006-446X 2011 10-0001-021 1 2 1. 201800 2. 201800 2001 2010 80% 8 5 O 613. 43 R 969 A 1857 1912 1980 20 1 1. 1 SOREMARK 1960 12 d 1 SANGSTER 1983 10 d MAY 1992 8 ~ 14 d 6 ~ 8 d RAUWS 1975 91 mg /kg 3 d VOBECKY 1996 13. 54 d 325 h PAVELKA 2000 6. 81 d 163. 4 ± 16. 3 h 6. 98 d 167. 4 ± 3. 4 h 8. 24 d 197. 8 ± 22. 2 h RAUWS 1 2011-09 -05 1

1 y ml / h kg x mg /d y 2. 5 ml / h kg 0. 3 ml / h kg y = 0. 143 + 0. 046 x r = 0. 994 7 10 PAVELKA 2 Wistar 5 Br - Cl - HCO3 - ClO - 4 SCN - 14 d 82 Br 24 Na 82 Br 24 Na 2 1 3 1 Br Cl 1 Na / mg d -1 Br Na Br /Na 1 49. 4 ± 5. 4 229 ± 35 256 ± 44 0. 89 52. 6 ± 6. 5 153 ± 24 159 ± 40 0. 96 2 41. 3 ± 5. 3 248 ± 0 240 ± 8 1. 03 142. 3 ± 11. 7 104 ± 23 124 ± 29 0. 84 3 39. 8 ± 2. 2 319 ± 31 295 ± 128 1. 08 142. 0 ± 12. 4 330 ± 12 99 ± 4 4 37. 8 ± 4. 2 325 ± 18 321 ± 147 1. 01 114. 7 ± 42. 8 181 ± 15 202 ± 33 0. 89 5 35. 8 ± 6. 9 248 ± 7 278 ± 132 0. 89 61. 4 ± 9. 8 175 ± 30 185 ± 78 0. 95 1 Br Na 3. 5 ± 0. 2 mg /kg 588 ± 33 mg /kg 2 1 ~ 5 Br - Cl - HCO3 - ClO4 - SCN - 3 4 Br Na y = 312. 951 5 x - 1. 451 2 r = - 0. 746 5 5 Br Na y = 1. 096 9 x - 30. 850 6 r = 0. 974 0 2

PAVELKA 3 82 Br γ 2 44 h 269 h 2 /d / /d / 12 269 ± 22 4M + 4F 30 96 ± 10 5 21 133 ± 9 4M + 4F 42 126 ± 16 5 21 a 105 ± 8 4M + 4F 70 133 ± 14 5 70 b 44. 3 ± 4. 5 6 1 Na Br Cl 1 696 ± 138 9. 7 ± 1. 0 2 900 ± 110 mg /kg 2 12 d 82 Br 3 a 16 d b 4 M F PAVELKA 4 9 5 17 d 82 Br 50 μg /g NaBr 3 3 NaI Tl γ 94. 3 ± 14. 6 h 235. 0 ± 88. 9 h 15 197. 8 ± 22. 2 h 3 3

3 10 4 cpm g -1 4. 57 ± 0. 23 135. 6 ± 13. 4 * 3. 88 ± 0. 17 152. 5 ± 12. 2 0. 74 ± 0. 04 99. 6 ± 10. 9 ** 1. 81 ± 0. 06 111. 0 ± 8. 5 ** 1. 04 ± 0. 04 94. 8 ± 9. 2 ** 1. 15 ± 0. 09 140. 0 ± 16. 8 3. 44 ± 0. 16 127. 6 ± 12. 0 ** 2. 60 ± 0. 32 170. 0 ± 37. 7 2. 80 ± 0. 69 235. 0 ± 88. 9 3. 24 ± 0. 15 134. 3 ± 12. 6 * 3. 61 ± 0. 13 147. 2 ± 10. 4 5. 64 ± 0. 69 153. 2 ± 34. 9 2. 16 ± 0. 09 109. 4 ± 9. 9 ** 1. 52 ± 0. 14 116. 5 ± 22. 8 * 3. 16 ± 0. 20 94. 3 ± 14. 6 ** 1 197. 8 ± 22. 2 h * P < 0. 05 **P < 0. 01 2 y x y = 102. 000 9 + 9. 283 9 x r = 0. 558 6 1. 2 - C max T max - AUC V d t T MRT CL 1 1999 4 10 18 90 mg - 5 10 ~ 40 s 21 ± 11 s 4

4 /mg C max / μg L -1 T max t T CL L -1 WRT AUC /μg h L -1 5 90 240. 68 1. 44 5. 88 1 484. 9 90 211. 58 1. 50 5. 63 1 501. 6 6 90 169. 03 1. 20 0. 49 7. 07 213. 70 1 267. 1 90 163. 20 1. 44 0. 69 7. 97 267. 20 1 317. 7 7 75 176. 46 3. 80 11. 75 40. 13 16. 17 1 969. 2 8 60 66. 50 2. 54 0. 43 4. 74 424. 0 60 67. 60 2. 18 0. 56 4. 84 426. 5 9 90 294. 10 1. 71 8. 65 2 090. 5 90 297. 90 1. 52 9. 50 2 012. 4 10 90 171. 90 1. 30 0. 60 6. 90 0. 12 0. 30 828. 2 11 30 69. 66 1. 95 7. 77 577. 3 30 67. 89 1. 89 7. 61 574. 8 12 60 91. 30 2. 39 0. 60 3. 78 591. 6 60 90. 20 2. 19 0. 66 4. 81 673. 6 13 60 84. 70 1. 70 7. 90 712. 5 60 81. 20 1. 80 8. 30 671. 1 14 90 195. 20 1. 30 6. 69 9. 30 1 375. 0 90 177. 80 1. 50 6. 91 9. 68 1 371. 2 15 90 169. 60 1. 60 6. 77 1 215. 3 90 170. 30 2. 10 6. 50 1 281. 4 16 60 84. 70 1. 70 7. 95 638. 7 60 81. 20 1. 80 8. 30 591. 5 5 18 90 mg 珋 x ± s 珋 x ± s 1. 3 ± 0. 3-1 0. 27 ± 0. 12 / μg L -1 171. 9 ± 53. 9-1 0. 42 ± 0. 28 0. 6 ± 0. 2 / L h -1 0. 12 ± 0. 05 6. 9 ± 2. 7 0. 3 ± 0. 1 /L 1. 47 ± 0. 76 0 ~ 24 h - /μg h L -1 785. 2 ± 278. 1-1 0. 32 ± 0. 12 0 ~ - /μg h L -1 828. 2 ± 315. 4 5

4 8 12-16 9 11 5 6 12 T max T 1. 69 ± 0. 34 h 7. 15 ± 1. 24 h 3. 8 h 11. 75 h 16. 17 h 2 6 19 20 10 mg 7 AUC 0 ~ 36 h 101. 5 ± 19. 1 % 6 C max /mg / μg L -1 T max T CL / L h -1 WRT AUC /μg h L -1 17 10 73. 8 1. 02 8. 06 600. 9 10 69. 7 0. 88 8. 68 571. 9 18 5 31. 5 1. 66 7. 06 340. 6 5 33. 4 1. 51 6. 64 325. 5 19 10 66. 2 0. 59 7. 11 24. 0 9. 80 469. 1 10 59. 3 0. 81 7. 04 24. 2 9. 87 460. 5 20 10 27. 2 4. 00 10. 30 15. 40 483. 1 10 56. 8 2. 60 11. 70 916. 0 21 7. 8 55. 4 0. 76 7. 10 458. 7 22 10 27. 5 4. 40 10. 30 20. 1 15. 50 506. 1 10 53. 7 1. 30 9. 90 19. 2 12. 60 530. 2 20 58. 8 3. 00 11. 10 16. 5 16. 50 936. 6 20 52. 4 0. 90 10. 10 16. 2 18. 50 889. 7 6 T max T 3. 75 ± 0. 60 h 10. 85 ± 0. 68 h T max T 1. 05 ± 0. 36 h 7. 97 ± 1. 31 h 20 10 mg 10 7 d 12 6

22 20 10 mg 8 R 3. 4 ± 1. 4 7 C max μg L -1 66. 2 ± 16. 7 59. 3 ± 16. 9 T max h 0. 59 ± 0. 28 0. 81 ± 0. 56 T h 7. 11 ± 0. 91 7. 04 ± 0. 84 MRT h 9. 80 ± 1. 35 9. 87 ± 1. 18 CL L h -1 24. 0 ± 6. 2 24. 2 ± 5. 1 Vd L 180. 1 ± 77. 7 201. 1 ± 75. 0 AUC 0 ~ 36 h μg h L -1 453. 5 ± 132. 8 445. 6 ± 87. 8 AUC 0 ~ μg h L -1 469. 1 ± 140. 3 460. 5 ± 92. 2 F 1 % 101. 8 F 2 % 101. 9 F 1 F 2 AUC 0 ~ 36 h AUC 0 ~ 8 C max 27. 5 ± 7. 9 53. 7 ± 12. 7 V d 296. 8 ± 41. 8 272. 5 ± 40. 9 T max 4. 4 ± 1. 5 1. 3 ± 1. 2 AUC 0 ~ 60 h 496. 3 ± 59. 5 522. 8 ± 67. 3 T 10. 3 ± 0. 9 9. 9 ± 1. 1 AUC 0 ~ 506. 1 ± 62. 2 530. 2 ± 67. 3 MRT 15. 5 ± 1. 3 12. 6 ± 1. 7 HVD 1 2 C max 15. 4 ± 1. 7 5. 4 ± 2. 5 CL 20. 1 ± 2. 5 19. 2 ± 2. 5 R 3. 4 ± 1. 4 1 7 2 HVD 1 2 C max 1 2 C max h R > 1. 5 3 5-23 -26 40 mg 9 40 mg 50. 0 ± 4. 9 μg /L 50. 0 ± 4. 9 μg /L 3. 15 ± 0. 22 h 38. 7 ± 1. 6 h - 2 252 ± 292 μg h L -1 5 h 7

9 /mg C max / μg L -1 T max T AUC 0 ~ 132h /μg h L -1 AUC 0 ~ /μg h L -1 23 40 47. 3 3. 3 36. 3 1 892. 8 2 069. 9 24 1 40 57. 4 2. 78 39. 1 2 364. 5 2 616. 8 2 40 54. 4 3. 00 40. 4 2 351. 1 2 636. 5 25 40 47. 7 3. 2 38. 8 1 876. 9 2 085. 0 40 46. 1 3. 2 37. 6 1 894. 6 2 097. 4 26 40 45. 6 3. 4 40. 2 2 008. 4 4 27 18 28 9 6 3 2 60 mg 2 9 d 10 T T max 11 10 C max μg L -1 150. 9 ± 56. 9 148. 9 ± 47. 4 T max h 2. 4 ± 1. 0 1. 9 ± 0. 5 T h 8. 72 ± 1. 62 8. 56 ± 1. 64 K 10 h -1 0. 49 ± 0. 07 0. 26 ± 0. 07 CL L h -1 57. 2 ± 18. 8 50. 4 ± 15. 6 V d L 707. 5 ± 215. 1 612. 3 ± 205. 5 MRT 0 ~ t h -1 9. 6 ± 0. 6 9. 8 ± 0. 9 MRT 0 ~ h -1 10. 6 ± 0. 7 10. 9 ± 1. 3 AUC 0 ~ t μg h L -1 1 119. 1 ± 315. 2 1 267. 6 ± 364. 8 AUC 0 ~ μg h L -1 1 140. 1 ± 321. 4 1 292. 3 ± 397. 7 DF 1. 90 ± 0. 30 C av μg L -1 71. 5 ± 20. 1 K 10 DF C av 8

11 C max 0. 133 ± 0. 03 0. 329 ± 0. 106 * MRT 0 ~ t 37. 9 ± 6. 9 46. 7 ± 7. 1 * T max 2. 6 ± 0. 9 2. 4 ± 0. 9 MRT 0 ~ 5. 5 ± 1. 9 T 26. 6 ± 7. 4 33. 2 ± 9. 7 AUC 0 ~ t 4. 5 ± 1. 3 12. 9 ± 4. 8 * K 10 0. 034 ± 0. 010 0. 057 ± 0. 009 * MRT 0 ~ 4. 9 ± 1. 4 14. 2 ± 5. 7 * CL 8. 7 ± 2. 3 3. 2 ± 1. 2 * DF 0. 95 ± 0. 29 V d 323. 7 ± 76. 1 147. 8 ± 19. 6 * C av 0. 23 ± 0. 08 1 10 2 * P < 0. 05 12 27 28 12 C max / μg L -1 T max T AUC / μg L -1 27 183. 9 2. 1 14. 4 2 307 216. 7 2. 2 17. 2 2 057 28 150. 9 2. 4 8. 7 1 140 148. 9 1. 9 8. 6 1 292 1 2 3 60 mg 5 13 29 31 32 119. 7% 97. 8% 106. 0% 13 /mg C max / μg L -1 T max T AUC / μg L -1 28 32 25. 44 1. 28 3. 07 147. 6 32 22. 70 1. 14 2. 83 123. 3 29 8 22. 50 2. 50 4. 21 152. 3 30 16 20. 00 1. 35 7. 13 61. 6 16 21. 70 0. 81 7. 59 60. 2 31 16 35. 10 1. 00 6. 12 125. 8 9

13 1. 5 T max 4. 67 h 6 14 14 t T C max / μg L -1 T max AUC / mg L -1 33 5. 5 43. 2 4. 4 3. 3 199 34 2. 4 43. 8 4. 5 2. 6 199 35 2. 1 43. 2 5. 9 3. 4 424 400 mg 1. 9 42. 4 5. 9 3. 1 423 33-34 18 400 mg - K α T max C max 15 100. 2 ± 4. 9 % 400 mg 4. 54 mg /L 4. 37 mg /L 2. 6 h 3. 3 h 24 h 2. 46 ± 0. 36 mg /L 2. 53 ± 0. 35 mg /L 3. 16 ± 0. 37 3. 13 ± 0. 50 5 ~ 6 d 7 mg /L 4 mg /L MIC 90 2 mg /L 400 mg 1 200 mg 7 ~ 10 d 35 Hyprim 400 mg 43. 2 ± 4. 8 h 42. 4 ± 4. 3 h 33 100. 3 ± 12. 7 % 15 A mg L -1 5. 22 ± 5. 54 3. 29 ± 3. 89 t h 2. 38 ± 1. 99 5. 54 ± 6. 24 B mg L -1 3. 49 ± 0. 51 3. 48 ± 0. 64 T h 43. 8 ± 6. 2 43. 2 ± 8. 4 α h -1 0. 409 ± 0. 248 0. 274 ± 0. 198 K α h -1 1. 28 ± 0. 72 * 0. 84 ± 0. 27 β h -1 0. 016 ± 0. 002 0. 017 ± 0. 003 V d L 73. 3 ± 14. 6 82. 6 ± 14. 8 C max mg L -1 4. 54 ± 0. 33 * 4. 37 ± 0. 36 CL L h -1 1. 78 ± 0. 31 1. 84 ± 0. 27 T max h 2. 60 ± 0. 70 ** 3. 30 ± 0. 30 AUC mg h L -1 199. 0 ± 25. 9 198. 9 ± 27. 0 * P < 0. 05 **P < 0. 01 7 10

36 16 16 n = 12 n = 12 n = 12 n = 12 t min 1. 7 ± 1. 4 1. 3 ± 0. 5 AUC mg h L -1 43. 3 ± 8. 1 30. 8 ± 9 T min 54. 7 ± 22. 0 48. 3 ± 11. 5 MRT min 60. 9 ± 27. 9 56. 3 ± 13. 1 V c ml kg -1 62. 7 ± 26. 1 40. 3 ± 11. 8 CL ml kg min -1 4. 4 ± 1. 9 4. 2 ± 1. 8 V ss d ml kg -1 196. 2 ± 40. 9 * 166. 5 ± 33. 2 1 V c V ss d 2 * P < 0. 05 3 0. 1 mg /kg 35 17 17 n = 12 n = 12 n = 12 n = 12 t 1. 4 ± 0. 7 1. 6 ± 0. 4 AUC 32. 3 ± 10. 6 30. 8 ± 8. 9 T 56. 9 ± 10. 1 67. 3 ± 12. 2 MRT 58. 9 ± 12. 5 56. 3 ± 13. 4 V c 29. 5 ± 23. 4 48. 7 ± 25. 8 CL 3. 7 ± 0. 9 * 5. 2 ± 1. 0 V ss d 147. 2 ± 31. 3 * 196. 5 ± 36. 2 1 16 2 * P < 0. 05 3 0. 1 mg /kg 8 37 1. 5 mg /kg 1. 1 min 10% 25% 75% 10. 5 min 12. 8 min 20. 4 min 7. 6 min 18 / 0. 377 0. 168 0. 120 18 / ml kg -1 81. 6 /min 4. 5 / ml kg -1 62. 6 /min 24. 0 / ml kg -1 11. 0 /min 105. 0 / ml kg -1 41. 0 /ml kg min -1 7. 0 11

1 ~ 3 h 5 ~ 40 h 19 19 T max T 1 11 21 1. 75 ± 0. 37 6. 88 ± 1. 49 2 1 1 3. 8 11. 75 1 6 9 1. 05 ± 0. 36 7. 97 ± 1. 31 2 3 4 3. 75 ± 0. 60 10. 85 ± 0. 68 1 4 6 3. 15 ± 0. 22 38. 73 ± 1. 57 1 2 4 1. 90 ± 0. 36 12. 22 ± 4. 29 1 4 6 1. 35 ± 0. 59 5. 16 ± 2. 0729 1 3 4 3. 10 ± 0. 36 43. 2 ± 0. 57 1 2 4 0. 95 ± 0. 13 1 1 1 1. 75 1 2 2 80 20 20 * 1915 1950 0 0 1981 1990 1 2 1951 1960 0 0 1991 2000 10 5 1961 1970 0 1 2001 2010 36 53 1971 1980 0 0 47 61 + 2. 1 ED 50 ED 90 ED 95 T 1 T 1 - ED 50 ED 90 ED 95 21 ED 95 3 22 1 7 12

21 μg /kg ED 50 ED 90 ED 95 2002 150 298 359 38 2004 178 296 342 39 2004 204 334 384 40 2005 210 358 411 41 2007 202 421 478 42 2009 141 239 275 43 WIERDA 1994 350 180 ± 30 324 ± 62 371 ± 63 2002 21. 9 41. 9 50. 4 38 WIERDA 1994 55. 0 21. 9 41. 9 52. 7 ± 3. 3 2004 19. 0 38. 9 44 MIRAKHUR 1992 22. 4 31. 8 35. 1 20. 7 ± 2. 4 31. 8 37. 0 ± 2. 7 KAPLAN 1999 302 45 KOPMAN 2000 390 750 WIERDA 1994 1 150 1 150 346 ± 62 950 ± 283 1 150 1 45 2 2. 2 T 1 T 1 T 1 0 T 0% T 1 0% 5% T 5% T 1 0% 25% T 25% T 1 0% 90% T 90% T 1 25% 75% T 25% ~ 75% 22 3. 7 3. 2 2. 8 1. 5 mg /kg 10. 7 ± 2. 8 min 0. 6 mg /kg 42. 7 min 0. 1 mg /kg 43. 3 min SCHIERE S 1997 13

22 min T 0% T 5% T 25% T 90% T 25% ~ 75% 2001 1. 43 20. 8 1 32. 5 48. 2 14. 0 46 2002 18. 7 25. 6 49. 2 14. 3 38 2004 1. 24 24. 8 42. 5 47 2004 1. 69 35. 6 21. 1 48 2005 1. 71 41 2006 13. 5 17. 1 49 2007 29. 7 42 2009 1. 42 23. 5 37. 0 56. 8 14. 0 43 2008 19. 9 23. 1 50 1. 50 ± 0. 20 22. 0 ± 2. 3 29. 5 ± 9. 5 51. 4 ± 4. 7 17. 3 ± 4. 0 2002 20. 8 29. 0 52. 3 7. 3 38 1997 1. 54 50. 5 12. 6 51 2003 3. 20 25. 0 2 44. 1 12. 9 52 2003 24. 0 34. 0 62. 0 21. 5 53 2006 1. 68 59. 8 20. 5 54 21. 14 ± 0. 92 23. 3 ± 2. 2 35. 7 ± 7. 7 35. 7 ± 7. 7 15. 0 ± 6. 0 2001 1. 45 6. 28 10. 03 20. 00 6. 36 46 2001 1. 10 12. 8 7. 6 55 2000 3 1. 60 10. 8 8. 3 56 1. 38 ± 0. 26 6. 28 11. 2 ± 1. 4 20. 0 7. 42 ± 0. 98 2000 2. 0 4. 0 52. 7 4 57 2004 3. 8 43. 7 65. 3 64. 0 58 1 2 3 4 2. 3 1 44 4 20 4 40 μg /kg 80 μg /kg 120 μg /kg ED 50 ED 90 ED 95 P < 0. 01 ED P < 0. 01 23 14

23 ED 50 94 ± 23 105 ± 22 145 ± 30 * 220 ± 40 * ED 90 158 ± 35 178 ± 54 240 ± 57 * 371 ± 91 * ED 95 183 ± 42 206 ± 74 282 ± 69 * 429 ± 114 * 1. 70 ± 0. 40 1. 37 ± 0. 38 * 1. 32 ± 0. 35 * 1. 27 ± 0. 40 * 23 ± 4 24 ± 4 23 ± 5 24 ± 7 46 ± 9 35 ± 7 * 32 ± 6 * 35 ± 9 * 75 ± 13 52 ± 10 * 48 ± 4 * 52 ± 11 * 21 ± 3 13 ± 5 * 11 ± 3 * 11 ± 4 * 1 20 2 ED μg /kg min 3 * P < 0. 01 P < 0. 01 51 n = 14 18 ~ 55 n = 17 65 ~ 81 24 T 1 24 P /μg kg min -1 9. 8 ± 1. 2 7. 9 ± 1. 7 < 0. 001 T 1 25% /min 14. 8 ± 6. 9 24. 9 ± 12. 3 0. 001 TOFR 0. 7 /min 45. 7 ± 14. 4 69. 1 ± 22. 8 0. 002 T 1 / μg L -1 2. 8 2. 2 < 0. 03 1 14 17 2 TOFR 4 52 55 P < 0. 05 25 25 min 1. 41 ± 0. 45 44. 9 ± 6. 3 9. 9 ± 3. 4 51 1. 61 ± 0. 59 * 56. 0 ± 9. 4 * 15. 3 ± 7. 3 * 1. 63 ± 0. 54 54. 2 ± 10. 4 16. 4 ± 8. 2 54 1. 72 ± 0. 52 65. 4 ± 12. 7 24. 5 ± 7. 1 1 12 2 * P < 0. 05 2 42 12 P < 0. 05 ED 50 ED 90 ED 95 26 15

26 ED 50 / μg kg -1 245 174 < 0. 01 ED 90 / μg kg -1 427 288 < 0. 01 ED 95 / μg kg -1 490 331 < 0. 01 /min 2. 25 ± 1. 27 1. 17 ± 0. 15 < 0. 05 P 48 0. 6 mg /kg 0. 15 mg 27 54 66 Ⅰ Ⅱ 28 P < 0. 01-0. 62-0. 73-0. 67-0. 71 27 T 1 25% min 28 ± 11 32 ± 13 * 41 ± 13 # 31 ± 12 37 ± 12 * 49 ± 13 # 29 ± 11 34 ± 12 * 42 ± 13 # 34 ± 11 40 ± 11 * 49 ± 12 # * P < 0. 05 # P < 0. 05 P < 0. 05 28 n = 36 n = 32 n = 36 n = 32 / 37 ± 3 33 ± 10 * /min 28 ± 11 40 ± 9 * /mg 18 ± 6 14 ± 4 * /min 18 ± 5 23 ± 9 * /min 21 ± 6 27 ± 7 * /min 50 ± 15 74 ± 22 * * P < 0. 05 3 45 30 3 A B 0. 5 MAC C 1. 0 MAC ED 50 ED 95 0. 5 MAC ED 50 25% ED 95 15% 1. 0 MAC ED 50 ED 95 60% 49% 29 16

29 μg /kg ED 50 ED 95 A 26. 4 ± 8. 4 49. 5 ± 14. 2 B 0. 5MAC 19. 8 ± 6. 8 * 42. 0 ± 13. 7 * C 1. 0MAC 10. 8 ± 5. 8 * 25. 3 ± 10. 5 * 1 MAC 2 ED y = a log x - b x y 3 A * P < 0. 05 B P < 0. 05 40 48 1. 5 mg /kg 30 5 min 4 n = 24 150 200 250 300 μg /kg 4 ED 50 198 ± 69 153 ± 35 * TOF 1 T 1 ED 90 318 ± 71 274 ± 66 * 5 min ED 95 367 ± 73 317 ± 80 * 15% 30 μg /kg n = 24 1 2 * P < 0. 05 4 4 TOF TCL 50 30 ASAⅠ ~ Ⅱ TCL TOF 9 mg /L 70 s 31 4. 5 mg /L 60% 31 P /s 24. 00 ± 7. 40 34. 00 ± 14. 00 0. 023 /s 73. 30 ± 26. 60 88. 70 ± 36. 20 0. 197 /min 116. 20 ± 24. 00 80. 40 ± 16. 80 0. 000 /min 19. 60 ± 8. 40 14. 50 ± 5. 50 0. 062 / mg kg -1 0. 86 ± 0. 09 0. 60 ± 0. 06 0. 000 /μg kg min -1 6. 48 ± 2. 28 8. 23 ± 2. 35 0. 048 /μg kg min -1 14. 52 ± 4. 75 11. 81 ± 2. 45 0. 059 17

2004 2004 2005 2006 5 43 18 3 32 ED 50 ED 90 ED 95 Dur 25 Dur 0. 8 32 ED 50 / μg kg -1 201 ± 59 * 258 ± 68 * 148 ± 48 ED 90 / μg kg -1 413 ± 107 * 530 ± 159 * 316 ± 116 ED 95 / μg kg -1 475 ± 155 * 598 ± 189 * 362 ± 149 Dur 25 /min 30 ± 8 * 22 ± 6 * 37 ± 8 Dur 0. 8 /min 46 ± 16 * 37 ± 13 * 56 ± 17 1 Dur 25 T 1 25% Dur 0. 8 T 4 /T 1 = 0. 8 2 * P < 0. 05 P < 0. 05 FISET P 1991 KATZ R L 1969 3 11 1 90 2 1 RAUWS A G. Pharmacokinetics of bromide ion an orerview J. Food chem Toxicol 1983 21 379-381. 2 PAVELKA S BABICKY A VOBECKY M. Biological half - life of bromide in the rat depends primarily on the magnitude of sodium intake J. Physiol Res 2005 54 639-644. 3 PAVELKA S VOBECKY M BABICKY A. Ascertainment of variations in the biological half - life of bromide and sodium ions in the rat by in vivo gamma - ray measuremcnt of 82 Br and 24 Na radionuclides J. Applied Radiation and Isotopes 2009 67 2110-2112. 4 PAVELKA S BABICKY A VOBECKY M et al. Bromide Kinetics and distribution in the rat. Ⅰ. Biokinetics of 82 Br - bromide J. Biol Trace Elem Res 2000 76 57-66. 5. J. 1999 10 4 168-169. 6. J. 1999 20 1 18

30-32. 7. RP - HPLC J. 2000 31 6 355-357. 8 J. 2006 17 12 923-925. 9. LC -MS J. 2006 46 6 43-46 50. 10. J. 2007 11 22 4321-4324. 11. J. 2007 38 9 638-640. 12. J. 2007 18 17 1324-1326. 13. J. 2008 19 14 1082-1083. 14. J. 2008 27 6 618-620. 15. J. 2008 19 5 341-343. 16. J. 2010 28 1 27-30. 17. J. 2002 18 4 284-286. 18. 2006 15 2 141-144. J. 19. LC - MS /MS J. 2007 32 1 33-37. 20. 3 214-217. J. 2007 10 21. J. 2007 22 4 410-412. 22. J. 2007 23 4 539-543. 23. 5 413-415. 24. 1 43-45. J. 2005 25 J. 2006 15 25. J. 2006 10 14 111-113. 26. J. 2009 20 1710-1712. 27. J. 2010 8 3 190-193. 28. J. 2010 26 19

4 293-296. 29 J. 1996 27 2 83-86. 30. J. 2000 18 6 543-545. 31. J. 2008 39 10 750-752 757. 32. HPLC - MS J. 2008 16 2 114-117. 33. J. 2000 9 6 357-359. 34. J. 2002 10 4 7-9. 35 J. 2001 6 1 53-55. 36. 1997 17 2 116-117. J. 37. J. 2006 32 6 588-589. 38. J. 2001 22 6 324-325. 39. - J. 2002 22 10 633-634. 40. J. 2004 24 11 973-975. 41. J. 2004 14 7 124-126. 42. J. 2005 25 1 11-14. 43. J. 2007 27 3 229-231. 44. J. 2009 29 3 203-206. 45. J. 2004 25 3 147-149. 46. J. 2003 18 1 122-123. 47. J. 2001 8 6 671-672. 48 ROGER E. J. 2004 24 1 7-9. 49. J. 2008 34 10 1066-1067. 50. TOF J. 2006 27 5 592-593. 51. J. 20

2008 8 4 342-344. 52. 1997 17 2 116-117. 53. 58 9661-9662. J. J. 2003 54. J. 2003 23 3 182-184. 55. J. 2006 32 6 588-589. 56. J. 2001 22 6 324-325. 57. J. 2000 21 3 164-167. 58. 15 1417-1418. J. 2002 23 59. J. 2004 24 5 345-347. Bromine Pharmacokinetics and Pharmacodynamics QIN Junfa 1 CHEN Panhua 2 1. Shanghai Institute of Applied Physics Chinese Academy of Sciences Shanghai 201800 China 2. Central Hospital of Jiading District Shanghai Shanghai 201800 China Abstract In this century bromine - containing drugs and their clinical applications of research has been an unprecedented development. In the 2001 2010 decade the literature of pharmacokinetics and pharmacodynamics of bromine - containing drugs in the total number of relevant literature is also accounted for about 80%. The present study focused on respiratory drugs and neuromuscular blocking drugs medication. A review with 59 references is given on the research situation of bromine pharmacokinetics and pharmacodynamics including the biological half - life of bromide and 8 kinds of drug pharmacokinetics and 5 drugs pharmacodynamics. Key words bromine trace elements pharmacokinetics pharmacodynamics 21