TABLE 2

AUC, Cmax, and Tmax values for CNS drugs in FVB and mdr1a/1b (-/-, -/-) mice after subcutaneous administration

Wild-type
mdr 1a/1b (-/-, -/-)
Drug Plasma
AUC
Plasma
AUC
Cmax
Tmax
 Plasma
Brain
CSF
Cmax
Tmax
 Plasma
Brain
CSF
ng/ml h ng · h/ml ng/ml h ng · h/ml
Buspirone 249 ± 26 0.5 208 ± 17 336 ± 25 10.5 ± 1.4 253 ± 27 0.5 274 ± 19* 551 ± 21 10.4 ± 1.6
Caffeine 3890 ± 240 0.5 3820 ± 141 3650 ± 170 300 ± 58 4030 ± 69 0.5 4520 ± 338 5000 ± 362 522 ± 112
Carbamazepine 654 ± 73 0.5 549 ± 42 415 ± 27 192 ± 12 781 ± 27 0.5 610 ± 17 494 ± 22 230 ± 16
Carisoprodol 81.2 ± 14.4 0.5 47.3 ± 8.7 31.1 ± 4.3 13.3 ± 2.2 118 ± 15 0.5 65.3 ± 8.8 52.6 ± 9.7 23.6 ± 3.0
Chlorpromazine 175 ± 17 0.5 476 ± 39 11,000 ± 1300 11.9 ± 3.2 170 ± 22 0.5 572 ± 38 16,600 ± 1500 7.1 ± 0.7
Citalopram 330 ± 10 0.5 300 ± 18 1540 ± 60 159 ± 23 362 ± 26 0.5 429 ± 35* 4170 ± 200 329 ± 15
Clozapine 189 ± 28 0.5 180 ± 21 746 ± 77 13.5 ± 1.5 136 ± 14 0.5 238 ± 38 1570 ± 130 21.6 ± 3.3
Cyclobenzaprine 244 ± 18 0.5 377 ± 21 4350 ± 460 21.5 ± 2.2 215 ± 22 0.5 366 ± 26 5770 ± 270 33.3 ± 3.1
Diazepam 214 ± 7 0.5 287 ± 20 562 ± 36 18.9 ± 2.7 188 ± 14 0.5 275 ± 21 636 ± 21 16.2 ± 2.1
Ethosuximide 902 ± 143 0.5 845 ± 89 956 ± 64 1350 ± 120 1120 ± 100 0.5 867 ± 66 943 ± 34 1390 ± 120
Fluoxetine 536 ± 27 0.5 994 ± 41 11,700 ± 400 31.1 ± 3.6 443 ± 34 0.5 964 ± 30 17,700 ± 500 38.2 ± 3
Fluvoxamine 292 ± 9 0.5 243 ± 10 1490 ± 40 14.1 ± 1.2 346 ± 11 0.5 316 ± 10 43,700 ± 200 29.5 ± 1.4
Haloperidol 263 ± 32 0.5 561 ± 33 7380 ± 390 80.7 ± 7.6 268 ± 28 0.5 684 ± 50 12,200 ± 700 124 ± 10.2
Hydrocodone 239 ± 24 0.5 162 ± 16 334 ± 13 90.1 ± 3.2 295 ± 32 0.5 232 ± 19 1050 ± 30 233 ± 17
Hydroxyzine 274 ± 10 0.5 245 ± 16 1890 ± 110 17.9 ± 1.8 366 ± 19 0.5 369 ± 14* 2790 ± 160 24.8 ± 1.7
Lamotrigine 2040 ± 100 1 7120 ± 520 7510 ± 550 1060 ± 70 2510 ± 100 1 7820 ± 870 8250 ± 920 1050 ± 90
Meprobamatea 120 ± 17 0.5 118 ± 16 49.9 ± 3.1 46.6 ± 11.1 98.4 ± 19.6 0.5 98.0 ± 22.7 67.6 ± 11.7 120 ± 53
Methylphenidate 226 ± 6 0.5 189 ± 6 2340 ± 110 210 ± 14 241 ± 14 0.5 197 ± 8 3750 ± 190 294 ± 18
Metoclopramide 281 ± 38 0.5 303 ± 31 369 ± 43 133 ± 18 347 ± 28 0.5 355 ± 24 2790 ± 170 419 ± 20
Midazolam 217 ± 64 0.5 172 ± 37 38.8 ± 8 9.58 ± 2.25 193 ± 46 0.5 209 ± 43 51.1 ± 8.8 17 ± 5.9
Morphine 256 ± 16 0.5 229 ± 11 105 ± 5 145 ± 11 243 ± 9 0.5 328 ± 23* 250 ± 6 254 ± 14
Nortriptyline 245 ± 18 0.5 312 ± 11 3520 ± 80 7.48 ± 0.63 307 ± 16 0.5 414 ± 12* 8430 ± 180 14.8 ± 1.3
Paroxetine 510 ± 25 0.5 1140 ± 40 3770 ± 70 16.7 ± 2.2 543 ± 58 0.5 1300 ± 70 9170 ± 200 32.2 ± 2.2
Phenytoin 2660 ± 60 0.5 7920 ± 230 5020 ± 90 1392 ± 77 2670 ± 240 0.5 9480 ± 390* 7360 ± 260 1730 ± 180
Propoxyphene 160 ± 9 0.5 221 ± 11 641 ± 32 44.9 ± 2.3 149 ± 12 0.5 211 ± 16 1600 ± 100 72.8 ± 7.1
Risperidone 398 ± 8 0.5 550 ± 14 429 ± 12 10.6 ± 1.9 406 ± 17 0.5 989 ± 22* 7930 ± 230 116 ± 11
9 OH-Risperidone 602 ± 27 0.5 1150 ± 50 69.4 ± 2.5 51.1 ± 4.4 575 ± 16 0.5 2300 ± 50* 2310 ± 60 975 ± 106
Selegiline 35.8 ± 1.6 0.5 66.0 ± 4.3 247 ± 14 28.9 ± 4.2 52.8 ± 5.9 0.5 86.7 ± 4.7* 357 ± 16 36.8 ± 2.6
Sertraline 139 ± 11 0.5 324 ± 21 7770 ± 180 1.68 ± 0.73b 124 ± 8 0.5 301 ± 14 8020 ± 270 1.28 ± 0.52b
Sulpiride 327 ± 13 0.5 346 ± 11 27.1 ± 1.3 13.1 ± 3.2 361 ± 14 0.5 476 ± 22* 73.1 ± 4.6 34.9 ± 10.5
Thiopental 1180 ± 140 0.5 2410 ± 90 857 ± 38 110 ± 7 786 ± 90 1 2290 ± 120 1010 ± 40 148 ± 8
Trazodone 443 ± 30 0.5 372 ± 31 225 ± 17 13.7 ± 2.1 631 ± 43 0.5 467 ± 49 253 ± 19 20 ± 1.6
Venlafaxine 486 ± 16 0.5 448 ± 28 1860 ± 70 184 ± 10 636 ± 55 0.5 579 ± 42* 4470 ± 170 427 ± 63
Zolpidem
302 ± 43
0.5
205 ± 26
58.7 ± 8
76.2 ± 11
409 ± 20
0.5
269 ± 14*
106 ± 10
119 ± 13

  • ↵* p < 0.05 vs. corresponding FVB AUC.

  • ↵ a Determined as metabolite formed following administration of carisoprodol.

  • ↵ b Data represent mean sertraline CSF concentrations (n = 5) observed at 0.5 and 1 h in FVR and mdr1a/1b (-/-, -/-), respectively.