Reboxetine pharmacokinetics

Dostert, P, Benedetti, MS and Poggesi, I (1997) Review of the pharmacokinetics and metabolism of reboxetine, a selective noradrenaline reuptake inhibitor. Eur. Neuropsychopharmacol. 1 (Suppl. 1) S23-S35. 

Maximal plasma concentrations occur 2 to 3 hours after oral administration of reboxetine (178). Reboxetine has linear pharmacokinetics over its clinically relevant dosing range and a half-life of approximately 12 hours. For this latter reason, a twice a day, equally divided dosing schedule was used during clinical trial development. Its clearance is reduced and half-life becomes longer as a function of advanced age (mean = 81 years of age) and renal and hepatic impairment ( 178, 322, 323). Reboxetine is principally metabolized by CYP 3A3/4 such that its dose should be reduced when used in combination with drugs that are substantial inhibitors of CYP (e.g., certain azole antifungals, certain macrolide antibiotics). Reboxetine itself, however, does not cause detectable inhibition of CYP 3A3/4 based on formal in vivo pharmacokinetic interaction studies as well as its own linear pharmacokinetics. 

Edwards DMF, Pillizzoni C, Breuel HP, et al. Pharmacokinetics of reboxetine in healthy volunteers. Single oral doses, linearity and plasma protein binding. Biopharm Drug Dispos 1995 16 443-460. 

Jannuzzo MG, Benedetti M, Duchene P. Pharmacokinetics of reboxetine in the elderly. 2nd International Symposium Meas Kinet In Vivo Drug Eff 1994 94-96(abst). 

Fiorentini F, Poggesi I, Jannuzzo MG, et al. Pharmacokinetics of reboxetine, a new selective nonradrenaline uptake inhibitor, in patients with various degrees of hepatic and renal insufficiency. Pharmacol Res 1997 35 239-239. 

Fleishaker JC, Mucci M, Pellizzoni C et al (1999) Absolute bioavailabihty of reboxetine enantiomers and effect of gender on pharmacokinetics. Biopharm Drug Dispos 20 53-57... 

Fleishaker JC, Herman BD, Pearson LK, Ionita A, Mucci M. Evaluation of the potential pharmacokinetic/ pharmacodynamic interaction between fluoxetine and reboxetine in healthy volunteers. Clin Drug Invest 1999 18 141-50. 

Fieishaker JC. Ciinicai pharmacokinetics of reboxetine, a seiective norepinephrine reuptake inhibitor for the treatment of patients with depression. Ciin Pharmacokinet 2000 39(6) 413-27. 

Antidepressants Reboxetine does not affect the pharmacokinetic parameters of fiuoxetine. 

Studies in healthy subjects have shown that reboxetine does not significantly interfere with the pharmacokinetics of aiprazoiam or iorazepam. 

Studies in healthy volunteers have shown that reboxetine 8 mg/day does not interfere with the pharmacokinetics of... 

Reboxetine seems to be an antidepressant that has negligible interference with the pharmacokinetics of other drugs thus, fewer drug-drug interactions are expected. It also may be possible to use reboxetine in combination with MAOIs, because it has no inhibitory effect on this enzyme, which would avoid tyramine-induced hypertensive reactions. 

No clinically relevant pharmacokinetic interaction appears to occur between risperidone and reboxetine. 

Reboxetine 8 mg daily was given to 7 schizophrenic patients taking risperidone 8 mg daily for a period of 3 weeks. Reboxetine had no significant effects on the pharmacokinetics of either risperidone or its active metabolite, 9-hydroxyrisperidone, suggesting that no additional precautions are necessary if reboxetine and risperidone are used together. ... 

The manufacturer of reboxetine recommends avoiding the concurrent use of potent CYP3A4 inhibitors as reboxetine levels may be increased. They also recommend avoiding the concurrent use of MAOk, because of the possible risk of hypertensive crises. The concurrent use of fluoxetine and reboxetine does not appear to alter the pharmacokinetics of either drug. 

A study in 30 healthy subjects given reboxetine 4 mg twice daily and fluoxetine 20 mg daily found no significant changes in the pharmacokinetics of either drug. ... 

A study in 10 healthy subjects who were of the CYP2D6 extensive metaboliser phenotype (the most commonly found phenotype) found that the pharmacokinetics of reboxetine 8 mg daily were not affected by a single 30-mg dose of dextromethorphan. ... 

The manufacturer points out the possibility of hypokalaemia if reboxetine is used with potassium-depleting diuretics. Experience with reboxetine in elderly patients suggests it reduces potassium by up to 0.8 mmol/L, starting after 14 weeks of use. They also suggest that the concurrent use of reboxetine and ei ot derivatives might result in increased blood pressure although no clinical data are quoted, and the concurrent use of lorazepam results in mild to moderate drowsiness and an orthostatic increase in heart rate, but no pharmacokinetic interaction occurs. ... 

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