Quetiapine pharmacokinetics

There is only one study in (open trial) examining the efficacy of quetiapine in the treatment of EOS (Mc-Conville et ah, 2000). Patientes were treated with 100 or 400 mg/day. Quetiapine was well tolerated and improved both positive and negative symptoms as determined by the BPRS, the CGI Scale, and the Modified SANS. Quetiapine pharmacokinetics were dose proportional in adolescents and resembled those reported in adult patients. The most common side effects in the study were postural tachycardia and insomnia. The EPS occurred and improved during the course of treatment. There were no serious adverse events or clinically important changes in hematology or clinical chemistry. 

Grimm SW, RichtandNM, Winter HR, Stams KR, Reele SB. Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics. BrJ Clin Pharmacol (2006), 61, 58-69,... 

Quetiapine is metabolized by hepatic CYP 3A3/4. Concurrent administration of cytochrome P450-inducing drugs, such as carbamazepine, decreases blood levels of quetiapine. In such circumstances, increased doses of quetiapine are appropriate. Quetiapine does not appreciably affect the pharmacokinetics of other medications. Pharmacodynamic effects are expected if quetiapine is combined with medications that also have antihistaminic or a-adrenergic side effects. Because of its potential for inducing hypotension, quetiapine also may enhance the effects of certain antihypertensive agents. 

TABLE 5-27. Pharmacokinetics of risperidone, olanzapine, quetiapine, and ziprasidone... 

In a brief review, emphasis has been placed on pharmacokinetic interactions between neuroleptic drugs and benzodiazepines, as much information on their metabolic pathways is emerging (629). Thus, CYP3A4, which plays a dominant role in the metabolism of benzodiazepines, also contributes to the metabolism of clozapine, haloper-idol, and quetiapine, and plasma neuroleptic drug concentrations can rise. 

The authors suggested that since the doses of quetiapine and fluvoxamine were relatively low and since they are metabolized by different CYP isozymes, this was probably not a pharmacokinetic interaction. Instead, they suggested that it may have been caused by dopamine-serotonin disequilibrium. 

Because of the frequency of co-administration of benzodiazepines with neuroleptic drugs, it is important to consider possible adverse effects that can result from such combinations. In a brief review, emphasis has been placed on pharmacokinetic interactions between neuroleptic drugs and benzodiazepines, as much information on their metabolic pathways is emerging (166). Thus, the enzyme CYP3A4, which plays a dominant role in the metabolism of benzodiazepines, also contributes to the metabolism of clozapine, haloperidol, and quetiapine, and neuroleptic drug plasma concentrations can rise. Intramuscular levomepromazine in combination with an intravenous benzodiazepine has been said to increase the risk of airways obstruction, on the basis of five cases of respiratory impairment the doses of levomepromazine were higher in the five cases that had accompanying airways obstruction than in another 95 patients who did not (167). 

Quetiapine (53) is the only dibenz(l,4)thia-zepine derivative currently available in the United States. Very few publications have been devoted to its biotransformation and pharmacokinetics (473,474). Much of the following information has been obtained from data on file from the manufacturer (475). 

Quetiapine exhibits dose proportional linear pharmacokinetics within the clinical dose range with accumulation that is predictable on multiple dosing. Clearance of quetiapine is largely through hepatic metabolism with a... 

Loose binding to striatal D2-like receptors clozapine, quetiapine, risperidone, sertindole, olanzapine (but may be a pharmacokinetic rather than pharmacodynamic effect). 

Postural hypotension and possibly drowsiness may be increased when alcohol is given with quetiapine. Quetiapine does not appear to affect the pharmacokinetics of alcohol. 

Haloperidol 7.5 mg twice daily and risperidone 3 mg twice daily for 9 days had no significant effect on the pharmacokinetics of quetiapine 300 mg twice daily in the same study. However, there is a case report de-... 

Wong YWJ, Yeh C, Thyrum PT, The effects of concomitant phenytoin administration on the steady-state pharmacokinetics of quetiapine. J Clin Psychopharmacol (2001) 21, 89-93. 

Quetiapine 150 mg three times daily was given to 7 psychotic men with cimetidine 400 mg three times daily for 4 days. There were some slight alterations in the pharmacokinetics of the quetiapine, but these were within the intraindividual changes seen and so were not considered significant. There would therefore appear to be no reason for avoiding concurrent use. 

The pharmacokinetics and pharmacodynamic effects of a single 2-mg dose of lorazepam were studied in 10 men taking quetiapine 250 mg three times daily. It was found that the maximum serum lorazepam levels were not significantly changed by quetiapine, and the alterations in the performance of a number of psychometric tests were small and considered not to be clinically relevant. ... 

Po in SG, Thyrum FT, Alva G, Carreon D, Yeh C, Kalali TV Arvanitis LA Effect of fluoxetine and imipramine on the pharmacokinetics and tolerability of die antipsychotic quetiapine. J Clin Psychopharmacol (2002) 22,174-82. 

Strakowski SM Keck PE, Wong YWJ, Thyrum PT, Yeh C. The effect of multiple doses of cimetidine on die steady-state pharmacokinetics of quetiapine in men widi selected psychotic disorders. J Clin Psychopharmacol (2002) 22,201 -5. 

Winter HR, Earley WR, Hamer-Maansson JE, Davis PC, Smith MA. Steady-state pharmacokinetic, safety, and tolerability profiles of quetiapine, norquetiapine, and other quetiapine metabolites in pediatric and adult patients with psychotic disorders. J Child Adolesc Psychopharmacol 2008 18(1) 81-98. 

Davis, P.C. Wong, J. Gefvert, O. Analysis and pharmacokinetics of quetiapine and two metabolites in human plasma using reversed-phase HPLC with ultraviolet and electrochemical detection, J.Pharm.Biomed.Anal., 1999,20, 271-282. 

A study of 30 mood disorder patients switched from quetiapine IR to XR reported the switch was tolerated by most patients with discontinuation in only two patients [204 ]. Early side effects included early/central insomnia wi day drowsiness (16.7%), increased appetite and weight (8.4%), mild asthenia (4.2%) and constipation (4.2%). A series of studies were conducted to characterise the pharmacokinetics of quetiapine ER which was foxmd to be generally well tolerated with a safety profile comparable to quetiapine IR, though with less initial sedation [205 ]. 

Bui K, Earley W, Nyberg S. Pharmacokinetic profile of the extended-release formulation of quetiapine fumarate (quetiapine XR) clinical implications. Curr Med Res Opin 2013 29(7) 813-25. 

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