Pharmacokinetics of quetiapine in elderly patients with selected psychotic disorders.
OBJECTIVE
To assess the pharmacokinetics and tolerability of quetiapine in elderly patients with selected psychotic disorders.


METHODS
This was a multicentre, open-label, 27-day, rising multiple-dose trial. Descriptive statistics summarised plasma quetiapine concentrations and pharmacokinetic parameters by trial day. A two-way analysis of variance was used to evaluate all pharmacokinetic parameters, and 90% confidence intervals of the mean differences were calculated.


METHODS
Antipsychotic drugs taken prior to the study period were discontinued on day 1. Quetiapine treatment began on day 3. Doses were increased stepwise, starting at 25mg three times daily and reaching 250mg three times daily by day 21.


METHODS
Twelve patients (age 63-85 years) with schizophrenia, schizoaffective disorder or bipolar disorder.


RESULTS
Key assessments included quetiapine plasma concentrations, and neurological and safety evaluations. Under steady-state conditions, the 100 and 250mg doses of quetiapine were not significantly different in terms of dose-normalised area under the plasma concentration-time curve within an 8-hour dose administration interval, or in dose-normalised minimum plasma concentration (C(min)) at the end of a dose administration interval. The morning C(min) values for the seven discrete dose amounts evaluated also increased linearly with dose. The apparent oral clearance, volume of distribution and half-life did not change as a function of dose. There were no serious adverse events. The most common adverse events were postural hypotension (n = 6), dizziness (n = 5) and somnolence (n = 4).


CONCLUSIONS
While quetiapine was well tolerated at doses up to 250mg three times daily, the potential for reduced clearance, as well as the adverse effects of postural hypotension and dizziness, indicated that quetiapine should be introduced at lower doses and titrated at a relatively slower rate in patients > or =65 years.
Jaskiw
George E
GE
Psychiatry Service 116A(B), Louis Stokes Cleveland V.A. Medical Center, 10000 Brecksville Road, Brecksville, OH 44141, USA. gxj5@case.edu
Thyrum
Per T
PT
Fuller
Matthew A
MA
Arvanitis
Lisa A
LA
Yeh
Chiao
C
D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000493:pharmacokinetics*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D000069348:Quetiapine Fumarate
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate