TABLE 3

Correlation of P450 activities with the metabolism rates of buspirone in a panel of human liver microsomes Buspirone (5 μM) was incubated separately with 16 individual HLM.


Metabolism Reactions

P450 Isoform

Regression Coefficient (r2)
Metabolite Formationa
Overall Buspirone Metabolismb
1-PP
3′-OH
6′-OH
5-OH
N-oxide
7-Ethoxyresorufin O-dealkylation 1A2 0.06 0.09 0.07 0.12 0.09 0.09
Coumarin 7-hydroxylation 2A6 0.25 0.25 0.24 0.21 0.18 0.01
S-Mephenytoin N-demethylation 2B6 0.41 0.32 0.50 0.32 0.49 0.40
Diclofenac 4′-hydroxylation 2C9 0.10 0.10 0.09 0.11 0.06 0.03
S-Mephenytoin 4′-hydroxylation 2C19 0.36 0.32 0.31 0.28 0.44 0.35
Dextromethorphan O-demethylation 2D6 0.08 0.08 0.08 0.06 0.09 0.11
Chlorzoxazone 6-hydroxylation 2E1 0.08 0.12 0.08 0.09 0.09 0.13
Testosterone 6β-hydroxylation
3A4
0.96***
0.92***
0.93***
0.85***
0.86***
0.92***
  • a Data presented in this table were averaged from analyses of duplicate incubations. Statistical significance of the correlation between metabolism rates and P450 enzyme activities is denoted by ***ρ <0.0005

  • b The rate of the overall metabolism was calculated based on the conversion of buspirone to the total metabolite peaks