Risperidone pharmacokinetics

Sommers DK, Snyman JR, van Wyk M, Blom MW, Huang ML, Levron JC. Lack of effect of amitriptyline on risperidone pharmacokinetics in schizophrenic patients. IntClin Psychopharmacol (1991) 12, 141-5. 

Risperidone (11) was also included among a a 1-adrenergic receptor antagonists to study a quantitative structure-activity relationship (99BMC2437). A pharmacophore model for atypical antipsychotics, including 11, was established (00MI41). An increased plasma level of 11 and 9-hydroxyrisperidone (12) was observed in combination with paroxetine (01 MI 13). The effect of vanlafaxine on the pharmacokinetics of 11 was reported (99MI13). 

Zhou, Z. L. et al. (2006). Multiple dose pharmacokinetics of risperidone and 9-hydroxyrisperidone in Chinese female patients with schizophrenia. Acta Pharmacol. Sin., 27, 381-6. 

Byerly M, DeVane L. Pharmacokinetics of Clozapine and Risperidone A Review of Recent Literature. J Clin Psychophar-macol 1996 16(2) 177-187. 

Casaer, R, Walleghem, D., Vandenbussche, L, Huang, M.-L., and DeSmedt, G. (1994) Pharmacokinetics and safety of risperidone in autistic children [abstract]. Pediatr Neurol 11 89. 

Byerly MJ, DeVane CL Pharmacokinetics of clozapine and risperidone a review of recent literature. J Clin Psychopharmacol 16 177-187, 1996... 

Among the reports on overlapping or combining clozapine and risperidone, some pharmacokinetic interactions have been reported ( 100, 103,104 and 105). 

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

Risch SC, Jackson C, Ware M, et al. Case reports of combined clozapine and risperidone pharmacotherapy pharmacokinetic and pharmacodynamic interactions. Poster presentation at the 33rd Annual Meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico, December 1994. 

Tyson SC, Devane CL, Risch SC. Pharmacokinetic interaction between risperidone and clozapine [Letter]. Am J Psychiatry 1995 152 1401-1402. 

A pharmacokinetic interaction of risperidone with fluoxetine has been reported (SEDA-22, 71). When 10 schizophrenic patients stabilized on risperidone 4-6 mg/ day took fluoxetine 20 mg/day for concomitant depression the mean plasma risperidone concentration increased from 12 to 56 ng/ml at week 4 the concentration of 9-hydroxyrisperidone was not significantly affected (51). One patient dropped out after 1 week because of akathi-sia associated with a markedly increased plasma risperidone concentration. 

In an open, 30-day trial, the pharmacokinetics, safety, and tolerability of a combination of risperidone 4 or 6 mg/ day with fluoxetine 20 mg/day were evaluated in 11 psychotic inpatients (52). CYP2D6 genotyping showed that three were poor metabolizers and eight were extensive metabolizers. The mean AUC of risperidone increased from 83 and 398 h.ng/ml to 341 and 514 h.ng/ml when risperidone was co-administered with fluoxetine in extensive and poor metabolizers respectively. However, despite this pharmacokinetic interaction, the severity and incidence of extrapyramidal symptoms and adverse events did not increase significantly when fluoxetine was added 10 of the 11 patients improved clinically. 

Bondolfi G, Eap CB, Bertschy G, Zullino D, Vermeulen A, Baumann P. The effect of fluoxetine on the pharmacokinetics and safety of risperidone in psychiatric patients. Pharmacopsychiatry 2002 35(2) 50-6. 

Spina E, Avenoso A, Scordo MG, Ancione M, Madia A, Gatti G, Perucca E. Inhibition of risperidone metabolism by fluoxetine in patients with schizophrenia a clinically relevant pharmacokinetic drug interaction. J Clin Psychopharmacol 2002 22(4) 419-23. 

Klockowski PM. Effect of venlafaxine on the pharmacokinetics of risperidone. J Clin Pharmacol 1999 39(3) 297-309. 

There were no changes in lithium pharmacokinetics when risperidone was substituted open-label for another neuroleptic drug in 13 patients (634). On the other hand, an 81-year-old man had an acute dystonic reaction 4 days after lithium was added to a regimen of risperidone, valproic acid, and benzatropine (635). 

Demling J, Huang ML, De Smedt G. Pharmacokinetics and safety of combination therapy with lithium and risperidone in adult patients with psychosis. Int J Neuropsychopharmacol 1999 2 S63. 

Eap CB, Bondolfi G, Zullino D, Bryois C, Fuciec M, Savary L, Jonzier-Perey M, Baumann P. Pharmacokinetic drug interaction potential of risperidone with cytochrome p450 isozymes as assessed by the dextromethorphan, the caffeine, and the mephenytoin test. Ther Drug Monit 2001 23(3) 228-31. 

Possible interactions between donepezil and risperidone, which are both metabolized by CYP2D6 and CYP3A4, have been studied (SEDA-26,65) (247). Of 24 healthy men (mean age 40 years) were assigned to risperidone 1 mg/day, donepezil 5 mg/day, or both, 20 reported at least one adverse event, mostly headache, nervousness, or somnolence. However, measures of pharmacokinetics showed no interaction. 

Severe parkinsonism with urinary retention occurred when fluoxetine 20 mg/day was added to risperidone 2 mg/day in a 46-year-old man with schizophrenia. Risperidone had been prescribed at this dose for 1 month without any adverse effects, and the authors considered that a pharmacokinetic interaction between fluoxetine and risperidone was the most likely mechanism (266). 

Ono S, Mihara K, Suzuki A, Kondo T, Yasui-Furukori N, Furukori H, de Vries R, Kaneko S. Significant pharmacokinetic interaction between risperidone and carbamazepine its relationship with CYP2D6 genotypes. Psychopharmacology (Berl) 2002 162(1) 50 1. 

Zhao Q, Xie C, Pesco-Koplowitz L, Jia X, Parier J-L. Pharmacokinetic and safety assessments of concurrent administration of risperidone and donepezil. J Clin Pharmacol 2003 43 180-6. 

An open comparison of donepezil and risperidone, alone or in combination, in 24 healthy men showed no significant pharmacokinetic differences (88). Adverse events such as headache, nervousness, and somnolence were minor and comparable in all groups. These results suggest that no clinically significant interactions occur between risperidone and donepezil at steady state. However, whether these conclusions can be extrapolated to the elderly patients with dementia, who may eliminate both donepezil and risperidone slowly, is uncertain. 

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