Table 1.
Michaelis-Menten Kinetic Constants for Terbinafine N-Dealkylation Pathways.a
| Steady-state kinetic constants for individual metabolites | ||||||||
|---|---|---|---|---|---|---|---|---|
| Pathway | Step | Substrate | Vmaxb | Km (μΜ) | Vmax/Km | Vmaxb | Km (μΜ) | Vmax/Km |
| Pathway 1 | 1 | terbinafine | TBF-Ac | N-methyl-1 -naphthyl-methylamine | ||||
| 33.7 ± 1.4 | 20.7 ± 4.2 | 1.63 | 218 ± 24 | 54.6 ± 17 | 3.99 | |||
| Pathway 2 | 2 | terbinafine | desmethyl-terbinafine | Formaldehyde | ||||
| 344 ± 16 | 30.1 ± 6.2 | 11.4 | high background masking rates | |||||
| 2A | desmethyl-terbinafine | TBF-Ac | 1-naphthyl-methylamine | |||||
| 132 ± 15 | 133 ± 32 | 1.05 | below limit of quantitatione | |||||
| 2B | desmethyl-terbinafine | 1-naphthaldehyde | 6,6-dimethyl-2-hepten-4-yn-1-amine | |||||
| 19.1 ± 1.4 | 68.4 ± 15 | 0.28 | undetected (unlabeled or labeled) | |||||
| Pathway 3d | 3 | terbinafine | 1-naphthaldehyde | N-methyl-6,6-dimethyl-2-hepten-4-yn-1-amine | ||||
| 6.38 ± 0.33 | 45.9 ± 9.7 | 0.14 | undetected (unlabeled or labeled) | |||||
a
Data fit best to the Michaelis-Menten equation over the Hill equation (P < 0.05). Values shown with standard deviation from mean.
b
Units are pmol/min/mg protein.
c
Kinetic results reflect underestimation of rates due to competing decay process as shown in Fig 2.
d
Pathway steps 3A and 3B not studied due to absence of authentic standards and low efficiency of previous step to obviate the significance of this pathway for TBF-A.
e
Limit of quantitation calculated as standard deviation of response divided by slope of standard curve.