Pharmacokinetics of breath 14CO2 after injection of [14C]N-methyl erythromycin
| Genotype | CERmax | Kbreath | AUC0–240 | CYP3A | |
|---|---|---|---|---|---|
| %ID/min | 1/min | %ID/min | pmol/mg | ||
| Treatment | |||||
| Control (n = 9) | (+ /+) | 0.47 ± 0.05 | 0.0128 ± 0.001 | 22.7 ± 0.7 | 31.9 ± 8.6 |
| Dexamethasone (n = 3) | (+ /+) | 0.69 ± 0.08 | 0.0118 ± 0.002 | 40.0 ± 1.1 | 268.6 ± 30.5 |
| PCN (n = 3) | (+ /+) | 0.81 ± 0.09 | 0.0126 ± 0.002 | 34.3 ± 1.2 | 200.2 ± 37.9 |
| DEX + TAO (n = 3) | (+ /+) | 0.23 ± 0.09 | 0.0124 ± 0.002 | 14.4 ± 1.2 | 312.3 ± 14.7 |
| 4-h ERMBT | |||||
| Mdr1 (n = 4) | (+ /+) | 0.47 ± 0.05 | 0.0128 ± 0.001 | 22.2 ± 0.9 | 29.8 ± 3.1 |
| Mdr1a (n = 3) | (− /−) | 0.51 ± 0.09 | 0.0137 ± 0.002 | 34.2 ± 2.6 | 24.3 ± 5.7 |
| Mdr1a/1b (n = 3) | (− /−) | 1.00 ± 0.09 | 0.0123 ± 0.002 | 42.3 ± 1.2 | 28.9 ± 6.6 |
| 30-min ERMBT | |||||
| Mdr1 (n = 4) | (+/+) | 0.58 ± 0.15 | 9.67 ± 1.61-a | 27.1 ± 1.7 | |
| Mdr1a (n = 3) | (− /−) | 0.95 ± 0.13 | 15.4 ± 1.41-a | 22.0 ± 9.5 |
Mice were injected with trace amounts of [14C]N-methyl erythromycin, and the rate of elimination of 14CO2 in the breath was calculated at 20-min intervals over 4 h or, for the 30-min ERMBT, at 5-min intervals over 30 min, and pharmacokinetic parameters determined in the indicated number of mice. Note: Statistical difference of breath14CO2 AUC0–240 in various mice after i.v. [14C]N-methyl erythromycin assessed by two-way and one-way ANOVA were as follows: 14CO2 AUC0–240in mdr1a/1b(+/+) control mice was significantly different from results in mice treated with DEX, PCN, or DEX + TAO wasP = .0001. The 14CO2 AUC0–240in mdr1a/1b(+/+) was significantly different from that in either mdr1a(−/−) or mdr1a/1b(−/−) mice (P = .0001). The 14CO2 AUC0–30in mdr1a/1b(+/+) was significantly different from that inmdr1a(−/−) mice (P = .0329).
ID, injected dose.
↵1-a AUC0–30.