Aripiprazole pharmacokinetics

Mallikaarjun S, Riesgo Y, Salazar F, BramerS,Xie J, Weston I. Time of dosing and food effect on aripiprazole pharmacokinetics. EurNeuropsychopharmacol (2003) S332,... 

A review of aripiprazole included a brief mention of no apparent pharmacokinetic interaction with lithium (624). 

Gibiansky, E., Gibiansky, L., and Bramer, S. Comparison of NONMEM, bootstrap, jackknife, and profiling parameter estimates and confidence intervals for the aripiprazole population pharmacokinetic model. Presented at American Association of Pharmaceutical Scientists Annual Meeting, Boston MA, 2001. 

Thus, valproate is often used to reduce the risk for clozapine-induced seizures. Carbamazepine can potentially increase the risk for development of agranulocytosis when coadministered with clozapine, so this combination should be avoided. Carbamazepine increases renal clearance of olanzapine by about 45% and reduces its half-life by about 20%. To date, no pharmacokinetic interactions have been reported between aripiprazole and valproate. 

To date, no pharmacokinetic interactions have been reported between aripiprazole and lithium. 

To date, the combined olanzapine-warfarin regimen has not revealed any pharmacokinetic interactions. No interactions have been reported to date between aripiprazole and... 

Lithium does not affect the pharmacokinetics of aripiprazole to a clinically significant extent... 

Aripiprazole plasma levels are increased by inhibitors, and decreased by inducers, of CYP3A4. Quinidine increases aripiprazole levels. The manufacturers advise caution with drugs that can prolong the QT intervaL Food and famotidine do not have a clinically relevant effect on the pharmacokinetics of aripiprazole, and aripiprazole does not affect the pharmacokinetics of dextromethorphan, omeprazole, and warfarin. 

A study in 39 healthy subjects who received 15 mg aripiprazole either after fasting, or 5 minutes after a high-fat breakfast, found no significant changes in the pharmacokinetics of aripiprazole. ... 

CitromeL, JosiassenR,BarkN, Salazar DE,Mallikaarjun S. Pharmacokinetics of aripiprazole and concomitant lithium and v proate. J CUn Pharmacol (2005) 45, 89-93. 

Drug-drug interactions SSRIs Aripiprazole had no effects on the pharmacokinetics of escitalopram, fluoxetine, paroxetine, sertraline, or venlafaxine either in healthy subjects ( =63) or in patients with major depressive disorder ( =498) [69. Point estimates for mean plasma concentration ratios indicated no substantial effect of aripiprazole on any antidepressant escitalopram 0.97 (0.91-1.03), fluoxetine 1.18 (1.05-1.32), paroxetine 0.73 (0.60-0.89), sertraline 0.96 (0.89-1.04), or venlafaxine 0.97 (0.89-1.05). 

Boulton DW, Balch AH, Royzman K, Patel CG, Berman RM, Mallikaarjun S, Reeves RA. The pharmacokinetics of standard antidepressants with aripiprazole as adjunctive therapy studies in healthy subjects and in patients with major depressive disorder. J Psychopharmacol 2010 24 537-46. 

Susceptibility factors Hepatic or renal impairment Two open, single-dose studies have been conducted to investigate whether the pharmacokinetics of aripiprazole are altered in individuals with hepatic or renal impairment [70 j. In study 1, six subjects with normal hepatic function and 19 with hepatic impairment (mild, n = 8 moderate, n = 8 severe, n = 3) received a single dose of aripiprazole 15 mg. The same dose was used in study 2, in seven patients with normal... 

Metamfetamine The results of a doubleblind study of potential interactions of intravenous metamfetamine (15 and 30 mg) with oral aripiprazole (15 mg) have been published [72 ]. The effects of aripiprazole on abstinence-related craving and cue-induced craving were also evaluated. Participants included non-treatment-seeking metamfetamine-dependent patients who took aripiprazole (n = 8) or placebo (n = 8) for 2 weeks. Aripiprazole had no effect on cue-induced metamfetamine craving, but was associated with increased craving independent of metamfetamine dose, euphoria, and amphetamine-like effects after metamfetamine. Aripiprazole reduced the increase in systolic blood pressure after metamfetamine, but it had no other effects on cardiovascular responses to metamfetamine. Aripiprazole did not alter the pharmacokinetics of metamfetamine. The adverse events tended to be equally distributed between the two groups, except for tremor (n = 4) and restlessness n = 3), which were more common in those who took aripiprazole. 

Mallikaarjun S, Shoaf SE, Boulton DW, Bramer SL. Effects of hepatic or renal impairment on the pharmacokinetics of aripiprazole. Clin Pharmacokinet 2008 47 (8) 533 2. 

Nakamura A, Mihara K, Nagai G, Suzuki T, Kondo T. Pharmacokinetic and pharmacodynamic interactions between carbamazepine and aripiprazole in... 

Drug-drug interactions The pharmacokinetics of aripiprazole, with and without coadministration of SSRIs, were compared according to CYP2D6 genotypes [93. Paroxetine decreased systemic clearance of aripiprazole by 58% and 23% in CYP2D6 extensive metaboUzers and intermediate metabolizers, respectively, while fluvoxamine had no effect... 

Azuma J, Hasunuma T, Kubo M, Miyatake M, Koue T, Higashi K, et al. The relationship between clinical pharmacokinetics of aripiprazole and CYP2D6 genetic polymorphism effects of CYP enzyme inhibition by coadministration of paroxetine or fluvoxamine. Eur J Clin Pharmacol 2012 68(l) 29-/37. 

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