Club drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate

Smith, Kelly M.; Larive, Lisa L.; Romanelli, Frank

doi:10.1093/ajhp/59.11.1067

Cited by 184 publications

(115 citation statements)

References 55 publications

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“…Flunitrazepam is primarily metabolized by CYP3A4 and 2C19. Ritonavir coadministration may result in flunitrazepam toxicity including hypotension, confusion, and aggressive behavior (Smith et al 2002). Other benzodiazepines, such as lorazepam, oxazepam, temazepam, and diazepam, are metabolized by non-CYP3A4 enzymes such as uridine 5′-diphosphate glucuronosyltransferase (UGT), UGT1A1, UGT1A3, and UGT2B7, but can also undergo drug interactions with antiretrovirals.…”

Section: Recreational Drugs and Antiretroviral Agentsmentioning

confidence: 99%

MDR- and CYP3A4-Mediated Drug–Drug Interactions

Pal

Mitra

2006

Jrnl Neuroimmune Pharm

168

123

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P-glycoprotein (P-gp), multiple drug resistance associated proteins (MRPs), and cytochrome P450 3A4 together constitute a highly efficient barrier for many orally absorbed drugs. Multidrug regimens and corresponding drug-drug interactions are known to cause many adverse drug reactions and treatment failures. Available literature, clinical reports, and in vitro studies from our laboratory indicate that many drugs are substrates for both P-gp and CYP3A4. Our primary hypothesis is that transport and metabolism of protease inhibitors (PIs) and NNRTIs will be altered when administered in combination with azole antifungals, macrolide, fluroquinolone antibiotics, statins, cardiovascular agents, immune modulators, and recreational drugs [benzodiazepines, cocaine, lysergic acid dithylamide (LSD), marijuana, amphetamine (Meth), 3,4-methylenedioxymethamphetamine (MDMA), and opiates] due to efflux, and/or metabolism at cellular targets. Therefore, such drug combinations could be a reason for the unexpected and unexplainable therapeutic outcomes. A number of clinical reports on drug interaction between PIs and other classes (macrolide antibiotics, azole antifungals, cholesterol lowering statins, cardiovascular medicines, and immunomodulators) are discussed in this article. MDCKII-MDR1 was employed as an in vitro model to evaluate the effects of antiretrovirals, azole antifungals, macrolide, and fluroquinolone antibiotics on efflux transporters. Ketoconazole (50 muM) enhanced the intracellular concentration of (3)H ritonavir. The inhibitory effects of ketoconazole and MK 571 on the efflux of (3)H ritonavir were comparable. An additive effect was observed with simultaneous incorporation of ketoconazole and MK 571. Results of (3)H ritonavir uptake studies were confirmed with transcellular transport studies. Several fluroquinolones were also evaluated on P-gp-mediated efflux of (3)H cyclosporin and 14C erythromycin. These in vitro studies indicate that grepafloxacin, levofloxacin, and sparfloxacin are potent inhibitors of P-gp-mediated efflux of 14C erythromycin and (3)H cyclosporin. Simultaneous administration of fluoroquinolones and macrolides could minimize the efflux and metabolism of both of the drugs. Effects of erythromycin and ketoconazole on carbamazepine metabolism were examined. Formation of 10,11-epoxy carbamazepine, a major CBZ metabolite, was significantly inhibited by these agents. Therefore, drug efflux proteins (P-gp, MRPs) and metabolizing enzyme (CYP450) are major factors in drug interactions. Overlapping substrate specificities of these proteins result in complex and sometimes perplexing pharmacokinetic profiles of multidrug regimens. Drug-drug interactions with PIs and other coadministered agents for human immunodeficiency virus (HIV) positive population have been discussed in light of efflux transporters and metabolizing enzymes. This article provides an insight into low and variable oral bioavailability and related complications leading to loss of therapeutic activity of MDR and CYP 450 substrates.

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Section: Recreational Drugs and Antiretroviral Agentsmentioning

confidence: 99%

MDR- and CYP3A4-Mediated Drug–Drug Interactions

Pal

Mitra

2006

Jrnl Neuroimmune Pharm

168

123

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“…Norketamine is the major metabolite of ketamine in vivo [10]. Ketamine, an antagonist of NMDA receptor, produces post-hypnotic emergence reactions such as prolonged hallucination and delirium, which therefore has led to its abuse as a recreational drug [11]. Ketamine misuse has been reported in many countries [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

The establishment of a highly sensitive method in detecting ketamine and norketamine simultaneously in human hairs by HPLC-Chip–MS/MS

Zhu

Leung

Ting

et al. 2011

Forensic Science International

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“…The cataleptic state brought on by administration of ketamine can also produce stupor and sedation, that together with possible amnesia and difficulty in fighting off an assailant, has led to its recent implication in drug-facilitated sexual assault (DFSA) [7,8]. DFSA incidents are often reported later than 24 h after the alleged assault, when very little drug will remain in the victim.…”

Section: Introductionmentioning

confidence: 99%