Predicted in vivo intestinal formation clearance and extraction ratio of nor-LAAM and dinor-LAAM
| nor-LAAM from LAAM | dinor-LAAM from LAAM | dinor-LAAM from nor-LAAM | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Vmax1/Km1 | CL | ERb | ERp | Vmax1/Km1 | CL | ERb | ERp | Vmax1/Km1 | CL | ERb | ERp | |
| ×10−3 | ml/min | % | ×10−3 | ml/min | % | ×10−3 | ml/min | % | ||||
| Microsomes | 21 ± 5 | 65 ± 16 | 21 ± 6 | 33 ± 11 | 0.4 ± 0.1 | 1.2 ± 0.4 | 0.5 ± 0.1 | 0.9 ± 0.3 | 7 ± 2 | 22 ± 6 | 8 ± 2 | 15 ± 4 |
| CYP3A4 | 490 | 35 | 12 | 21 | 49 | 3.5 | 1.4 | 2.6 | 220 | 15 | 6 | 11 |
ER, extraction ratio assuming that drug distributes into red blood cells (ERb) or is restricted to plasma (ERp). ERb and ERp were calculated from the equation described in the text.Vmax1/Km1 is expressed as milliliters per minute per milligram of protein for microsomes and milliliters per minute per nanomole of P450 for CYP3A4. Microsomal values are the mean ± S.D. of three different microsomes as described in Table 3.