DOSTÁLEK, Miroslav, Eva HADAŠOVÁ, Mariana HANESOVÁ, Jana PISTOVČÁKOVÁ, Alexandra ŠULCOVÁ, Jan JUŘICA, Josef TOMANDL and Igor LINHART. Feet of methamphetamine on pharmacokinetics of dextromethorphan and midazolam in rats. (Effect of methamphetamine on pharmacokinetics of dextromethorphan and midazolam in rats.). Eur J Drug Metab Pharmacokinet. Switzerland,: Medicne et Hygiena, 2005, vol. 30, No 3, p. 195-201. ISSN 0378-7966.
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Basic information
Original name Feet of methamphetamine on pharmacokinetics of dextromethorphan and midazolam in rats.
Name in Czech Vliv metamfetaminu na farmakokinetiku dextrometorfanu a midazolamu.
Authors DOSTÁLEK, Miroslav (203 Czech Republic, belonging to the institution), Eva HADAŠOVÁ (203 Czech Republic, guarantor, belonging to the institution), Mariana HANESOVÁ (703 Slovakia), Jana PISTOVČÁKOVÁ (703 Slovakia, belonging to the institution), Alexandra ŠULCOVÁ (203 Czech Republic, belonging to the institution), Jan JUŘICA (203 Czech Republic, belonging to the institution), Josef TOMANDL (203 Czech Republic, belonging to the institution) and Igor LINHART (203 Czech Republic).
Edition Eur J Drug Metab Pharmacokinet, Switzerland, Medicne et Hygiena, 2005, 0378-7966.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30104 Pharmacology and pharmacy
Country of publisher Czech Republic
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 0.585
RIV identification code RIV/00216224:14110/05:00014064
Organization unit Faculty of Medicine
UT WoS 000232621200008
Keywords in English Midazolam; Methamphetamine; Cytochrome P-450; CYP3A1/2 isozyme
Tags CYP3A1/2 isozyme, cytochrome P-450, methamphetamine, midazolam
Changed by Changed by: doc. RNDr. Josef Tomandl, Ph.D., učo 47. Changed: 6/6/2012 08:38.
Abstract
Methamphetamine is the fourth most frequently cited drug of abuse on treatment centre admission records behind cocaine, heroin and marijuana. We investigated the effect of methamphetamine (10 mg/kg, i.p., once daily for six days) on the pharmacokinetics of midazolam a substrate for rat cytochrome P-450 3A. Animals received a single injection of midazolam (5 mg/kg) in tail vein 24 h after the last dose of methamphetamine and placebo. Validated HPLC method was used to quantify all compounds of interest. The elimination half-life (t1/2) and the area under the concentration-time curve of midazolam were significantly reduced by pretreatment with methamphetamine to 63.8 % and 66.3 of control value, respectively and the clearance of midazolam was significantly increased by methamphetamine pretreatment. The results showed that administration of methamphetamine significantly stimulated metabolic activity of CYP3A1/2. With regard to a high level of homology between human and rat CYP isoforms studied, the results may have clinical impact in pharmacotherapy of methamphetamine abusers.
Abstract (in Czech)
Cílem studie bylo popsat vliv opakovaného podávání metamfetaminu (10 mg/ kg, i.p., jednou denně po dobu 6ti dnů) na farmakokinetické parametry dextrometorfanu (markeru metabolické aktivity CYP2D2) a midazolamu (markeru metabolické aktivity CYP3A1/2). Poločas eliminace midazolamu a plocha pod koncentrační křivkou midazolamu byly opakovaným podáváním metamfetaminu statisticky významně zkráceny na 63.8 % resp. 66.3 % hodnoty kontrolní skupiny. Clearance midazolamu byla metamfetaminem statisticky významně zvýšena. Metamfetamin statisticky významně zvýšil aktivitu formy CYP3A1/2 a díky velké podobnosti potkaní a lidské formy se zjistěné výsledky mohou stát významné pro klinickou praxi.
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MSM 141100001, plan (intention)Name: Plasticita řídících systémů centrálního nervového systému a možnosti jejího ovlivnění
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