{'fraction_non_alphanumeric': 0.03077783995523223, 'fraction_numerical': 0.03749300503637381, 'mean_word_length': 4.96, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Midazolam is a phenobarbital-like cytochrome p450 inducer in rats.

Midazolam is almost exclusively metabolized by cytochrome P450 3A (CYP3A) isoenzymes. Therefore, midazolam is used as a probe to determine CYP3A levels in humans and rats. A prerequisite for longitudinal determination of CYP3A expression levels using midazolam as a probe is that midazolam itself has no effect on the expression of CYP3A. In the present study, we analyzed the mRNA levels and enzyme activities of the major CYP isoforms in the rat liver after intraperitoneal injection of midazolam (50 mg/kg) for 3 consecutive days. CYP3A1 mRNA levels were increased 4-fold in midazolam-treated animals compared with controls, whereas the mRNA levels of CYP3A2, CYP3A9, and CYP3A18 were not altered. The increase in CYP3A1 mRNA was accompanied by a 25% increase in microsomal testosterone 6beta-hydroxylation activity. More strikingly, CYP2B1/2 mRNA levels were increased 22-fold upon midazolam treatment, leading to an 11- to 95-fold enhancement of CYP2B enzyme activity. CYP2C6 mRNA levels were 4 times higher in midazolam-treated animals. Formation of 2alpha-hydroxy-testosterone, mainly catalyzed by CYP2C11, was 2.6-fold lower in liver microsomes from midazolam-treated animals. Midazolam induced CYP2E enzyme activity 2.5-fold at the post-transcriptional level. The induction of CYP2B1/2 mRNA levels by midazolam was dose-dependent (4.5-fold increase at 10 mg/kg). Induction of CYP3A1 and CYP2B expression was also observed in isolated rat hepatocytes cultured with 100 microM midazolam. We conclude that midazolam is a phenobarbital-like CYP inducer in rats. Induction of CYP3A1 by midazolam may have implications for the longitudinal use of midazolam as a probe for analysis of CYP3A expression levels in rats.