Effect of methamphetamine on cytochrome P450 activity.
Amphetamine-based drugs, including methamphetamine, are some of the most widely used illegal drugs in the world. Methamphetamine is metabolized by the cytochrome P450s, the latter also being involved in the metabolism of many drugs and other xenobiotics. The effect of methamphetamine pretreatment (10 mg kg-1, intraperitoneally once daily for 6 days) on the activity of the P450 enzymes was assessed both in the rat isolated perfused liver and in vivo. The rate of 4-hydroxydiclofenac production was significantly enhanced in vivo, indicating a possible stimulatory effect on P4502C6. Similarly, the kinetics of tolbutamide and dextromethorphan in isolated perfused rat liver indicate a significant increase in both P4502C6 and the P4502D subfamily. No significant changes in midazolam kinetic in the isolated perfused rat liver were observed. The potential for methamphetamine to cause drug interactions is of clinical relevance and, therefore, it warrants further investigation. Until further drug interaction experiments are accomplished, the co-administration of drugs with methamphetamine should be conducted with caution.
Dostalek
M
M
Department of Pharmacology, Institute of Chemical Technology, Prague, Czech Republic. miroslavdostalek@vandebilt.edu
Jurica
J
J
Pistovcakova
J
J
Hanesova
M
M
Tomandl
J
J
Linhart
I
I
Sulcova
A
A
D000818:Animals; D000697:Central Nervous System Stimulants / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D003915:Dextromethorphan / Q000493:pharmacokinetics; D004008:Diclofenac / Q000031:analogs & derivatives* / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008694:Methamphetamine / Q000493:pharmacokinetics*; D008874:Midazolam / Q000493:pharmacokinetics; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013255:Steroid 21-Hydroxylase / Q000378:metabolism*; D014044:Tolbutamide / Q000493:pharmacokinetics
D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D006993:Hypnotics and Sedatives; D007004:Hypoglycemic Agents; D004008:Diclofenac; D008694:Methamphetamine; D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; C089877:Cyp2c6v1 protein, rat; D000072467:Cytochrome P450 Family 2; D013255:Steroid 21-Hydroxylase; C108036:4'-hydroxydiclofenac; D008874:Midazolam