CYPs cytochrome testing

CYP. cytochrome P450 isoenzyme HIV, human immunodeficiency vims INR, International Normalized Ratio LFTs, liver function tests MAOI, monoamine oxidase inhibitor PT, prothrombin time TCA, tricyclic antidepressant. 

BUN, blood urea nitrogen CBC, complete blood cell count CNS, central nervous system CYP, cytochrome P-450 isoenzyme LFT, liver function test MAO, monoamine oxidase QTc, Q-T interval corrected for heart rate SCr, serum creatinine TMP-SMX, trimethoprim-sulfamethoxazole. 

Figure 5 Flowchart for initial and possible follow-up CYP inhibition studies. The first box represents the IC50 experiment with and without a 30-minute preincubation with NADPH (the highest concentration of test article is also preincubated for 30 minutes without NADPH). Remaining boxes depict possible outcomes and follow-up experiments. Abbreviations CYP, cytochrome P450 IC50, concentration of inhibition causing 50% inhibition.

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

H. and Pelkonen, O. (2006) Cytochrome P450 (CYP) inhibition screening comparison of three tests. European... 

The metabolism of 7V-nitrosodiethanolamine by a-hydroxylation, which is a cytochrome P450 (CYP)-mediated pathway, was not detected in liver preparations from uninduced male Fischer 344 rats (Farrelly et al., 1984,1987). The existence of a-hydroxylation was proved later, notably by the formation of glycol aldehyde in liver microsomes from rats pretreated with CYP2E1 inducers. The microsomal metabolism of N-nitrosodiethanolamine was slower by a-oxidation than by [3-oxidation (Loeppky, 1999). Bioactivation tests of jV-nitrosodiethanolamine in V79 Chinese hamster cells showed that cytotoxicity was observed only in cells transfected with human CYP2E1 but not in cells expressing CYP2B1 or in the controls (Janzowski et al., 1996 Loeppky, 1999). 

The cytochrome P450 (CYP) enzyme system is a key player in methadone metabolism, and research is aimed at discovering which isoenzymes have the most influence. Although its metabolism is complex and research is incomplete, methadone appears to be metabolized mainly by CYP2B6 [52-54]. Testing for this isoenzyme may help identify who is at risk for slow metabolism and, therefore, toxicity from drug accumulation. 

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