Concurrent administration of donepezil HCl and sertraline HCl in healthy volunteers: assessment of pharmacokinetic changes and safety following single and multiple oral doses

Nagy, Christa F.; Kumar, Dinesh; Perdomo, Carlos; Wason, Suman; Cullen, Edward I.; Pratt, Raymond D.

doi:10.1111/j.1365-2125.2004.01801.x

Cited by 24 publications

(15 citation statements)

References 34 publications

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“…Nagy et al [62] evaluated the safety and pharmacokinetics of donepezil HCl and sertraline HCl when administered separately and in combination. Plasma donepezil and SRT concentrations were determined by LC-MS. Safety was evaluated by physical and laboratory evaluations and the monitoring of adverse events.…”

Section: Ms Detectionmentioning

confidence: 99%

Analytical methodologies for the determination of sertraline

Bosch¹,

Ruiz-Sánchez²,

Rojas³

et al. 2008

Journal of Pharmaceutical and Biomedical Analysis

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Section: Ms Detectionmentioning

confidence: 99%

Analytical methodologies for the determination of sertraline

Bosch¹,

Ruiz-Sánchez²,

Rojas³

et al. 2008

Journal of Pharmaceutical and Biomedical Analysis

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“…Donepezil is primarily metabolized by the cytochrome P450 (CYP) isoenzymes 2D6 and 3A4 [14], but has only minimal inhibitory activity against them [15], and a low potential to interact with drugs that inhibit CYP 2D6 and CYP 3A4, e.g. sertraline [16], cimetidine and ketoconazole [15, 17].…”

Section: Introductionmentioning

confidence: 99%

Concurrent administration of donepezil HCl and levodopa/carbidopa in patients with Parkinson's disease: assessment of pharmacokinetic changes and safety following multiple oral doses

Okereke¹,

Kirby²,

Kumar

et al. 2004

Brit J Clinical Pharma

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AimThe use of acetylcholinesterase inhibitors for the treatment of comorbid Alzheimer's disease in Parkinson's disease (PD) patients stabilized on a levodopa regimen may potentially disrupt cholinergic balance. This randomized, double-blind, crossover study investigated the safety of, and possible drug-drug interaction between, donepezil HCl and levodopa/carbidopa. MethodsTwenty-five patients with PD who were taking physician-optimized doses of levodopa/ carbidopa (with daytime dosing intervals of 4-8 h) were administered once-daily doses of either donepezil HCl (5 mg) or placebo for 15 days, in two treatment periods, separated by a washout of at least 2 weeks. Some patients took a second dose of levodopa/carbidopa after 4 h, therefore subanalysis of the levodopa/carbidopa data was conducted up to 4 h and 8 h after dosing. Twenty-six healthy matched controls received open-label donepezil HCl only, for a single 15-day period. Blood samples were collected before, during and after the 15 doses of donepezil HCl for pharmacokinetic (PK) assessments. Pharmacokinetic parameters included maximum attained plasma drug concentration ( C max ), time at which C max is attained ( t max ), plasma drug concentration at steady state ( C ss ), and area under the drug concentration-time curve over the dosing interval. Safety assessments included monitoring adverse events, and the Unified Parkinson's Disease Rating Scale (UPDRS) motor examination. ResultsThe mean age of all subjects was 72.6 ± 1.3 years. Donepezil PK assessments of PD patients receiving levodopa/carbidopa were similar to the P K results from healthy controls who received donepezil HCl only (mean AUC 0 -12 h = 281.6 ± 17.6 and 268.6 ± 19.9 ng·h ml -1 , respectively). Carbidopa PK were not significantly altered by the concomitant administration of multiple doses of donepezil HCl, compared with when PD patients received placebo (mean AUC 0 -8 h = 921.8 ± 160 and 821.8 ± 113 ng·h ml -1 , respectively). Four hours after administration of donepezil HCl in PD patients, AUC 0 -4 h , C max and C ss of levodopa were higher than when PD patients received placebo ( P < 0.05). Eight hours after donepezil HCl, however, only C max and t max were observed to change compared with when PD patients received placebo (mean C max = 2652 ± 429 and 2077 ± 276 ng ml -1 , respectively; mean t max = 1.7 ± 0.4 and 2.9 ± 0.5 h, respectively; P £ 0.05). The number of PD patients who experienced at least one adverse event during the study (13/25) was higher when they C. S. Okereke et al. 4258 :S1 Br J Clin Pharmacol received donepezil HCl than when they received placebo (5/25), but was the same as healthy subjects who received donepezil HCl only (13/26). There were no significant differences in change from baseline on the UPDRS motor examination parameters in PD patients when they took donepezil HCl and when they took placebo. ConclusionsNo clinically significant drug-drug interactions between donepezil HCl and levodopa/ carbidopa were observed at steady state. The small changes in the pharmacok...

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“…Consistent with this, a report has described two elderly patients treated with paroxetine, at a dosage of 245 antianxiety drug interactions 20 mg/day, who developed gastrointestinal adverse effects (severe diarrhea), insomnia, agitation, confusion, and aggression after they received concomitant donepezil, 5 mg/day (Carrier, 1999). On the other hand, there is no evidence of a reciprocal metabolic interaction between sertraline and donepezil, as documented in an open-label, three-period crossover pharmacokinetic study in 19 healthy volunteers, coadministered sertraline (100 mg/day) and donepezil (5 mg/day) for 15 days (Nagy et al, 2004).…”

Section: Drugs For the Treatment Of Dementiamentioning

confidence: 99%