Table 3.
Relative bioavailability of TMZ and MTIC following intravenous and oral administration
| Mode of administrationa | Intrasubject CV (%) | Ratio estimatec,d i.v./p.o. (%) | 90% CI, % | ||
|---|---|---|---|---|---|
| i.v.b | p.o.b | ||||
| MTIC (n = 19) | |||||
| C max (μg/mL) | 0.28 | 0.28 | 13 | 98 | 91–105 |
| AUC (t f) (μg h/mL) | 0.84 | 0.82 | 9 | 103 | 98–108 |
| AUC (I) (μg h/mL) | 0.89 | 0.86 | 8 | 103 | 98–108 |
| TMZ (n = 19) | |||||
| C max (μg/mL) | 7.3 | 7.5 | 10 | 97 | 91–102 |
| AUC (t f) (μg h/mL) | 23.1 | 21.8 | 5 | 106 | 103–109 |
| AUC (I) (μg h/mL) | 24.6 | 23.4 | 5 | 105 | 102–108 |
TMZ, temozolomide; MTIC, 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide; i.v., intravenous; p.o., oral; CV, coefficient of variation; CI, confidence interval; C max, maximum concentration of drug after dosing; AUC (t f), area under the concentration–time curve from 0 h to time of final quantifiable sample; AUC(I), area under the concentration–time curve from 0 h to infinity
aThe dose of TMZ administered on pharmacokinetic sampling days (both i.v. and p.o.) was 150 mg/m2 per day
bModel-based (least-squares) geometric mean
c Based on log-transformed data using ANOVA model extracting the effects due to treatment, sequence, subject within sequence and period
dRatio of the mean value for i.v. to p.o. administration