Serum, fluoxetine

Kelly M, Perry P, Holstad S, et al. Serum fluoxetine and norfluoxetine concentrations and antidepressant response. TherDrug Monii 1989 11 165-170. 

Although each HPbC method has its own unique considerations, the following description of the determination of the fluoxetine in serum provides an instructive example of a typical procedure. 

Description of Method. Fluoxetine, whose structure is shown in Figure 12.31a, is another name for the antidepressant drug Prozac. The determination of fluoxetine and its metabolite norfluoxetine. Figure 12.31 b, in serum is an important part of monitoring its therapeutic use. The analysis is complicated by the complex matrix of serum samples. A solid-phase extraction followed by an HPLC analysis using a fluorescence detector provides the necessary selectivity and detection limits. 

The effects of buspirone are decreased when the drug is administered with fluoxetine Increased serum levels of buspirone occur if the drug is taken with erythromycin or itraconazole Should any of these combinations be required, the dosage of buspirone is decreased to 2.5 mg BID, and the patient is monitored closely. Venlafaxine blood levels increase with a risk of toxicity when administered witii MAOIs or cimetidine There is an increased risk of toxicity when trazodone is administered with the phenothiazines and decreased effectiveness of trazodone when it is administered with carbamazepine Increased serum digoxin levels have occurred when digoxin is administered with trazodone There is a risk for increased phenytoin levels when phenytoin is administered witii trazodone... 

Dixit B, Nguyen, H, Dixit VM. 1991. Solid-phase extraction of fluoxetine and norfluoxetine from serum with gas-chromatography-electron-capture detection. J Chromatogr B 563 379. 

Ulrich S. 2003. Direct stereoselective assay of fluoxetine and norfluoxetine enantiomers in human plasma or serum by two-dimensional gas-liquid chromatography with nitrogen-phosphorus selective detection. J Chromatogr B 783 481. 

Duverneuil and coworkers (2003) have developed a method for the determination of 11 of the most commonly prescribed non-tricyclic antidepressants and some of their metabolites these include paroxetine, fluoxetine, norfluoxetine, sertraline, citalopram, fluvoxamine mirtazapine, venlafaxine, and 0-des-methylvenlafaxine. The method involves an LLE procedure followed by an HPLC separation with photodiode-array UV detection at three different wavelengths (220, 240, and 290 nm). The total run time was 18 min. The extraction recoveries were calculated to be in the range of 74-109% and the lower limit of detection (LLOD) reported was 2.5-5 ng/ml. A method published by Tournel and associates (2001) also reported the simultaneous determination of several newer antidepressants by RP-HPLC with UV detection. The compounds were isolated from human serum using an LLE process. The LLOQ ranged from 15-50 ng/ml depending on the analyte of interest. The total run time for all compounds eluted was approximately 20 min. 

Waschgler R, Hubmann MR, Conca A, MoU W, Konig P. 2002. Simultaneous quantification of citalopram, clozapine, fluoxetine, norfluoxetine, maprotiline, desmethylmaprotiline and trazodone in human serum by HPLC analysis. Int J Clin Pharmacol Ther 40(12) 554-559. 

Rash and accompanying events Seven percent of patients taking fluoxetine have developed a rash or urticaria. Several other patients have had systemic syndromes suggestive of serum sickness. 

Drugs that can increase carbamazepine serum levels include cimetidine, danazol, diltiazem, erythromycin, felbamate, clarithromycin, fluoxetine, isoniazid, niacinamide, propoxyphene, ketaconazole, itraconazole, verapamil, valproate, troleandomycin, loratadine, nicotinamide, tricyclic antidepressants, SSRIs, nefazodone, protease inhibitors. 

L. T. Kerner, B. Cohen, P.F. Renshaw, A comparison of brain and serum pharmacokinetics of R-fluoxetine and racemic fluoxetine A 19-F MRS study. Neuropsychopharmacology 30 (2005) 1576-1583. 

Meltzer, H.Y., Young, M., Metz, J., Fang, V.S., Schyve, P.M., and Arora, R.C. (1979) Extrapyramidal side effects and increased serum prolactin following fluoxetine, a new antidepressant. J Neural Transm 45 165-175. 

Loof et al. (1995) reported the use of carbamazepine (300-1200 mg/day, serum levels 10-11.5 pg/mL) in 28 children and adolescents with sexual abuse histories. By treatment end, 22 of 28 patients were asymptomatic of PTSD. The remaining six were significantly improved in all PTSD symptoms except for continued abuse-related nightmares. Half of this cohort had com-orbid ADHD, depression, ODD or polysubstance abuse and were treated with concomitant medications, e.g., methylphenidate, clonidine, sertraline, fluoxetine, or imipramine. 

Welsh GS MMPl profiles and factors A and R. J CMn Psychol 21 43-47, 1965 Wenzel K, Meinhold H, Ruffenberg M Classification of hypothyroidism in evaluating patients after radioiodine therapy by serum cholesterol, Tj uptake, total T4, F T4 index, total Tj, basal TSH and TRH test. Fur J Chn Invest 4 141, 1974 Wernicke JF The side effect profile and safety of fluoxetine. J Chn Psychiatry 46 (3 sec 2) 59-67, 1985... 

Antacids reduce the absorption and enzyme-inducing drugs may decrease serum levels. Cimetidine and propranolol both increase serum levels. There can be competition for metabolic pathways by some tricyclic antidepressants (TCAs) and SSRIs (especially fluoxetine) which may increase serum levels. 

Fluvoxamine increases the systemic availability of oral melatonin, probably by reducing its first-pass clearance (34). In a crossover study in seven healthy subjects, serum melatonin concentrations were increased by fluvoxamine but not citalopram (35). In another study fluoxetine, paroxetine, citalopram, imipramine, and desipramine did not affect the biotransformation of melatonin at therapeutic concentrations in vitro (36). 

Orsulak, P. J., Kenney, J. T., Debus, J. R., Crowley, G., Wittman, P. D. Determination of the Antidepressant Fluoxetine and Its Metabolite Norfluoxetine in Serum by Reversed-Phase HPLC, with Ultraviolet Detection. Clin. Chem. 1988, 34, 1875-1878. 

Queiroz ME, Oliveira EB, Breton F et al (2007) Immunoaffinity in-tube solid phase microextraction coupled with liquid chromatography-mass spectrometry for analysis of fluoxetine in serum samples. J Chromatogr A 1174 72-77... 

Franceschi L, Faggiani A, Furlanut M (2009) A simple method to monitor serum concentrations of fluoxetine and its major metabolite for pharmacokinetic studies. J Pharm Biomed Anal 49 554-557... 

A 44-year-old man with depression was given hydroxyzine hydrochloride 100 mg/day, clonazepam 2 mg/ day, and citalopram 20 mg/day. Two years before he had tolerated fluoxetine for 6 months for an episode of depression, with good effect. After 7 weeks he developed weakness and weight loss. Physical examination was normal but the serum aspartate transaminase (AsT) was raised at 277 IU/L (reference range < 36 IU/1). His bilirubin was normal. Citalopram was withdrawn and the other drugs were continued intermittently 5 days later the serum aspartate transaminase had fallen by a half, and within 2 months it had returned to normal. 

Leibovitz A, Bilchinsky T, Gil I, Habot B. Elevated serum digoxin level associated with coadministered fluoxetine. Arch Intern Med 1998 158(10) 1152-3. 

Fluoxetine has been reported to increase serum digoxin concentrations (37). 

Several case reports and one in vitro study have suggested that combined administration of fluoxetine with phenytoin can significantly increase phenytoin serum concentrations, leading to toxicity (19,39,40). 

CALCIUM CHANNEL BLOCKERS SSRIs Reports oft serum levels of nimodipine and episodes of adverse effects of nifedipine and verapamil (oedema, flushing and i BP) attributed to t levels when co-administered with fluoxetine Fluoxetine inhibits CYP3A4-mediated metabolism of calcium channel blockers. It also inhibits intestinal P-gp, which may t the bioavailability of verapamil Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (lightheadedness, dizziness on standing, etc.). Consider reducing the dose of calcium channel blocker or using an alternative antidepressant... 

Sluzewska A, Rybakowski JK, Ladak M, Mackiewicz A, Sobieska M, Wiktorowicz K (1995) hiterleukin-6 serum levels in depressed patients before and after tieatment with fluoxetine. AunN Y Acad Sci 762 474 76. 

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