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Concurrent administration of donepezil HCl and risperidone in patients with schizophrenia: assessment of pharmacokinetic changes and safety following multiple oral doses.
- Source :
-
British journal of clinical pharmacology [Br J Clin Pharmacol] 2004 Nov; Vol. 58 Suppl 1, pp. 50-7. - Publication Year :
- 2004
-
Abstract
- Aim: This open-label, multiple-dose trial investigated the effect of concurrent administration of donepezil HCl with risperidone on the pharmacokinetics (PK) and safety profiles of both drugs.<br />Methods: Sixteen male patients with schizophrenia, who were receiving stable, physician-optimized risperidone (1-4 mg twice daily), and 15 healthy age- and weight-matched male controls, received donepezil HCl 5 mg daily for 7 days. Patients with schizophrenia remained on their physician-optimized dose of risperidone throughout the study. Pharmacokinetic parameters (C(max), t(max) and AUC) were assessed from plasma drug concentrations measured in blood collected before, during and after administration (for 12 h after risperidone on days 0 and 7, and for 24 h after donepezil HCl on day 7).<br />Results: The mean age of all the subjects was 38.5 years. Donepezil PK parameters were similar between patients taking donepezil HCl + risperidone (AUC(0-24 h) = 329.0 +/- 17.2 ng x h ml(-1)) and controls taking donepezil HCl alone (AUC(0-24 h) = 354.7 +/- 28.2 ng x h ml(-1)). Pharmacokinetic parameters for risperidone and 9-OH risperidone were not altered in patients with schizophrenia after 7 days of donepezil HCl administration (AUC(0-12 h) standardized by dose: risperidone = 59.6 +/- 16.3 ng.h ml(-1) at day 0, 56.0 +/- 15.8 ng x h ml(-1) at day 7; 9-OH risperidone = 162.1 +/- 19.2 ng x h ml(-1) at day 0, 163.3 +/- 15.0 ng x h ml(-1) at day 7). The most common adverse event in both treatment groups was diarrhoea (6/16 risperidone + donepezil HCl patients and 9/16 donepezil HCl only subjects). There were no significant changes in physical examination, ECG, vital signs or treatment-emergent abnormal laboratory values associated with either of the treatment regimens. No subject developed extrapyramidal side-effects following donepezil administration.<br />Conclusions: These results suggest that once-daily dosing of 5 mg donepezil HCl does not alter the PK of risperidone in patients with schizophrenia. The combination of risperidone and donepezil HCl was well tolerated.
- Subjects :
- Administration, Oral
Adult
Aged
Antipsychotic Agents adverse effects
Antipsychotic Agents pharmacokinetics
Area Under Curve
Cholinesterase Inhibitors adverse effects
Cholinesterase Inhibitors pharmacokinetics
Donepezil
Drug Combinations
Drug Interactions
Humans
Indans adverse effects
Indans pharmacokinetics
Male
Middle Aged
Piperidines adverse effects
Piperidines pharmacokinetics
Risperidone adverse effects
Risperidone pharmacokinetics
Antipsychotic Agents administration & dosage
Cholinesterase Inhibitors administration & dosage
Indans administration & dosage
Piperidines administration & dosage
Risperidone administration & dosage
Schizophrenia drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0306-5251
- Volume :
- 58 Suppl 1
- Database :
- MEDLINE
- Journal :
- British journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 15496223
- Full Text :
- https://doi.org/10.1111/j.1365-2125.2004.01817.x