Effects of Cytochrome P450 Inhibitors on Itraconazole and Fluconazole Induced Cytotoxicity in Hepatocytes

Table 1

ATP levels in rats hepatocytes after fluconazole or itraconazole incubations. Control and SKF 525A pretreated hepatocytes were exposed to various concentrations of fluconazole or itraconazole for 6 hours.

	ATP (nmol/10^6 cells)
Drug	Control hepatocytes	5 mg/kg SKF 525A pretreated hepatocytes	25 mg/kg SKF 525A pretreated hepatocytes
None (control)	27.1±3.5^ax	25.2±2.7^ax	23.2±2.9^ax
Fluconazole (mM)
0.001	30.1±4.5^ax	27.5±3.4^ax	26.2±4.1^ax
0.01	31.2±2.3^ax	27.2±2.1^ax	25.1±2.3^ax
0.1	24.6±0.7^bx	24.0±1.7^ax	20.2±5.2^ax
1.0	20.3±3.9^bcx	20.1±2.4^bx	18.5±6.7^ax
Itraconazole (mM)
0.001	29.2±3.1^ax	26.2±3.1^axy	21.2±3.9^ay
0.01	22.7±2.4^bx	19.3±2.8^bcy	16.2±2.5^by
0.1	16.3±3.5^cdx	15.7±3.9^cdx	12.3±2.0^by
1.0	13.2±0.9^dx	11.2±2.9^dx	7.2±3.1^cy

Values are mean  ± sd of 3 separate experiments. ^a–dMeans with different superscript differ significantly (𝑃<.05) in the same column. ^x-yMeans with different superscript differ significantly (𝑃<.05) in the same row.