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New Horizons in Science & Technology (NHS&T), Volume 1(2):27-32 ISSN 1929-2015 (Online)
International Network for Scientific & Industrial Information
Recent Studies on Pharmacokinetic of Citalopram and
Therapeutic Drug Monitoring
Zuhal Uckun
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ankara University, Tandogan-06100, Ankara, Corresponding author: ABSTRACT
Citalopram (CIT) is a potent and selective serotonin reuptake inhibitor in the central nervous system and widely
used to treat depression. There are some factors that affect the pharmacokinetics of citalopram, for example age,
renal and hepatic insufficiency, genetic polymorphism. The most important factor among them is genetic
polymorphism; which can change plasma concentrations of CIT and its metabolites. Therapeutic drug monitoring
(TDM) provides indirect measurement of drug concentration at the effector site, -plasma concentration of any drug
reflect concentration at the site of action. Therefore, TDM can be used by the physicians to optimize dosage
decisions, but only with a drug level in blood may always not help to reach a decisive conclusion. TDM results
should be supported by analysis of genotype. In line with this objective, this study reports a brief review about
pharmacokinetic of citalopram and therapeutic drug monitoring.

Key words
: Therapeutic drug monitoring, citalopram, pharmacokinetic
New Horizons in Science & Technology 1(2):27-32
bioavability is reported to be approximately 80% Citalopram (1-[3-(dimethylamino) propyl]- (Bezchlibnyk-Butler et al., 2000; Hiemke and 1- (4 - fluorophenyl) - 1, 3- dihydroisobenzofuran- Hartter, 2000). CIT is bound to protein in 80% 5carbonitrile; CIT) is a bicyclic phthalate compound (Milne and Goa, 1991) and thus interacts at specific approved in 1998 by the US Food and Drug protein-binding sites quite unlikely. It is widely Administration for the treatment of depression distributed among peripheral tissues, with the volume (Pollock, 2001). It is also proposed for the other of distribution of CIT, which is approximately central nervous system diseases such as anxiety, between 12 and 16 L/kg (Milne and Goa, 1991). CIT obsessive-compulsive disorders, bipolar disorders displays linear kinetics over the therapeutic dosage and various phobias (Pollock, 2001). CIT is marketed range of 10-60 mg/day, and peak plasma levels occur as a racemic compounds, which are both S-(+) and R- 2 to 4 hours after single or multiple doses (Baumann (-) enantiomers. The S-(+) enantiomer of CIT is pharmacologically active in relation to inhibition of serotonin reuptake versus the R-(-) enantiomer of Metabolism
CIT (Bezchlibnyk-Butler et al., 2000). Citalopram CIT is metabolized in liver by two N- has by far the highest selectivity for inhibiting demethylation steps, to demethylcitalopram (DCIT) serotonin reuptake over noradrenaline reuptake (Hiemke and Hartter, 2000; Owens et al., 2001). didemethylationcitalopram (DDCIT) by CYP2D6. Selective serotonin reuptake inhibitors (SSRIs) act by inhibiting the reuptake of serotonin into the the metabolites of the proponic acid derivative (CIT- presynaptic nerve terminal, enhancing synaptic PROP) and CIT-N-oxide occurs by oxidative deamination and by N-oxide, respectively (Gutierrez and Abramowitz, 2000, Unceta et al., 2011) (Figure PHARMACOKINETIC
detectable in the substantial amounts (Bezchlibnyk-Butler et al., 2000; Baumann and Larsen, 1995). The Absorption and Distribution
enhanced hydrophilicity of the metabolites limits CIT is well absorbed from gastrointestinal their ability to cross the blood-brain barrier. tract after oral administration. In contrast to the other Therefore, the metabolites of CIT are of minor SSRIs, the first-pass effect of CIT seems to be of minor importance, and for this reason, its oral New Horizons in Science & Technology 1(2):27-32
significant difference between two age groups Elimination
Lima et al. (2005) reported the mean plasma elimination. The distribution phase continues levels of CIT corrected for a 20 mg daily dose were approximately 10 hours. The elimination half-life 55% higher in the very elderly patients (>=80 year, (t1/2) has been determined to vary between 30 and 35 n=23) (65±30 ng/ml; p<0.001) and 38% higher in the hours for CIT, 50 hours for DCIT and 100 hours for elderly patients (65-79 year, n=57) (58±24 ng/ml; DDCIT (Baumann and Larsen, 1995). CIT can be p<0.001) when compared to the adult patients (=<64 administered once daily due to its relatively long year, n=48) (42±17 ng/ml). DCIT mean plasma level half-life (Bezchlibnyk-Butler et al., 2000). 20% of the was 38% higher (p<0.05) in the very elderly patients dose CIT is excreted unchanged in the urine (Joubert (22±10 ng/ml) when compared to the adult patients and Stein, 1999; Pollock, 2001). CIT and its (16±9 ng/ml). The mean plasma concentration of CIT metabolites are cleared primarily by the kidneys. + DCIT was 48% higher in the very elderly patients Renal clearance is estimated at 2.3 to 3.3 L per hour, (86±36 ng/ml; p<0.001) and 33% higher in the and systemic clearance ranges from 23 to 28 L per elderly patients (77±28 ng/ml; p<0.001) when hour (Noble and Benfield, 1997). Summary of compared to the adult patients (58±21 ng/ml). pharmacokinetic properties of citalopram is given in As a consequence, the studies above suggest that there are age-related pharmacokinetic effects. Therefore, it is recommended that elderly patients Table 1. Summary of pharmacokinetic properties of
Hepatic and Renal insufficiency
clearance of citalopram was reduced by 17%, and t1/2 was moderately increased; the peak plasma concentration was unaffected in patients with mild to moderate renal function impairment compared to normal subjects. In these patients, dosage adjustment is not recommended. Also, Joffe et al. (1998) reported oral clearance of citalopram was decreased by 37% and t1/2 had doubled in patients with impaired aAdapted from Baumann and Larsen, 1995; Noble and Benfield, hepatic function compared to normal subjects; the 1997; Joubert, A.F. and Stein, 1999; Bezchlibnyk-Butler et al., 2000. peak plasma concentration was unaffected. It is recommended that patients with reduced liver FACTORS ALTERING THE PHARMA-
function should receive lower initial doses. COKINETIC OF CITALOPRAM
Genetic polymorphisms in genes that encode
enzymes involved in metabolism of citalopram
citalopram are as follows; age, hepatic and renal insufficiency and genetic polymorphisms in genes citalopram are CYP2C19, CYP3A4 and CYP2D6. that encode enzymes involved in metabolism. Major metabolite of CIT is DCIT. Therefore, mutations in CYP2C19 and CYP3A4 genes are more important than those in CYP2D6 gene. Today, there are around 27 variant allele of subjects aged more than 60 years that CIT the area CYP2C19 and around 22 variant allele of CYP3A4 under the dose concentration curve (AUC) and half- ( life were increased in a single –dose study by 30% and 50%, respectively, and were increased in multiple-dose study by 23% and 30%, respectively. CYP2C19*3, CYP2C19*17. The effects of *2 and *3 Foglia et al (1997) found that DCIT-to-CIT ratio alleles (defective allele=def, i.e., CYP2C19*2 or *3) decreased significantly when compared to that show by slowing down citalopram metabolism. It was suggested that subjects carrying *2 and *3 alleles clearance for patients over 65 years of age was found 16.6 L/h whereas that for younger patients was found concentration of desmethylcitalopram to citalopram 25.2 L/h, and as a result there was statistically (MR) were determined to be 0.20±0.07, 0.15±0.05, New Horizons in Science & Technology 1(2):27-32
0.07±0.03 in subjects with CYP2C19*1/*1 genotype, THERAPEUTIC DRUG MONITORING
with CYP2C19*1/def , with CYP2C19 def/def, respectively, (P<0.001). Citalopram oral clearances The drug concentration in the blood depend in subjects with CYP2C19def/def genotypes were 42.9% and 33.3% reduction compared with the elimination of the drug. Drug metabolism, as well as CYP2C19*1/*1 groups, CYP2C19*1/def groups, other factors that affect the drug pharmacokinetic parameter, varies from one patient to another, and the Yu et al. (2003) reported that subjects with interindividual variability of drug metabolism can CYP2C19def/def genotypes had higher AUC0-∞ values, lower the oral clearance (CLoral) of concentrations of psychoactive drugs from standard citalopram than subjects with CYP2C19*1/*1, *1/def doses (Dahl and Sjogvist, 2000; Hiemke, 2008a,b,c). (P<0.01). Also, AUC0-∞ and Cmax of DCIT in TDM could be a useful tool in the following subjects with CYP2C19def/def genotypes were significantly lower than the values of subjects with CYP2C19*1/*1, *1/def genotypes (P<0.01). The CYP2C19*1/*1, *1/def genotypes was almost three non-response or occurrence of adverse effects at generally recommended doses CYP2C19def/def genotypes (P<0.01). suspicion of a particular metabolism in special Concerning CYP2C19*17 polymorphism, its results are controversial. The results of some studies showed pharmacokinetic of the drugs used for the study (Sim et al., 2006; Baldwin et al., 2008; Rudberg et al., TDM results can be used by the physicians 2008a; Wang et al., 2009), whereas those of other to optimize dosage decisions in order to maximize studies showed that polymorphism did not change efficacy and prevent toxicity, especially when pharmacokinetic of the drugs used for the study individuals are nonresponsive to treatment or (Ohlsson et al., 2008; Rudberg et al., 2008b). As a vulnerable to adverse reactions with standard doses result, it is reached that some of genetic due to age, disease states or drug interactions. The polymorphisms in genes that encode enzymes results of some TDM studies are present in Table 2-5, involved in metabolism of a drug can affect its without mentioning genetic profile of subjects pharmacokinetic, and thereby that *2 polymorphism participating in these studies. These results are limited due to the fact that plasma concentration may not always guarantee usefulness and meaningfulness of the information. Figure 1. The metabolism of citalopram (Unceta et al., 2011).
New Horizons in Science & Technology 1(2):27-32
Table 2. Plasma concentrations of CIT and DCIT at different daily doses (Reis et al., 2002).
Table 3. Plasma concentration of CIT and DCIT at different daily doses (Reis at al., 2003).
Table 4. Median values of CIT and DCIT at different daily doses (Reis et al., 2009).
Table 5. Plasma concentrations of CIT, DCIT, and DDCIT in 345 plasma samples of 258 depressive patients treated
with (10-360 mg/day) CIT (Le Bloc’h et al., 2003).

analysis. So that, the physician makes the patient's pharmacokinetic of citalopram, which are intrinsic treatment decision in more easier and more short factors but the most important factor is person’s time. This may also help physician in choosing the genetic profile. The results by Le Bloc’h et al (2003) right drug and the right starting dose for in time and Reis et al (2002, 2003, 2009) were reported according to daily doses used. * 2 polymorphism is known to slow the metabolism of citalopram, REFERENCES
precisely. By determining the genetic profile of subjects involved the studies, CIT plasma levels may Baldwin, R.M., Ohlsson, S., Pedersen, R.S., Mwinyi, be helpful to optimize therapy. If the information is considered in different way, daily dose range is Bertilsson, L. 2008. Increased omeprazole reduced, and more accurate min-max values and metabolism in carriers of the CYP2C19*17 allele; median are obtained. In conclusion, data such as a pharmacokinetic study in healthy volunteers. concentration measurements obtained by TDM should be supported with data obtained by genotype New Horizons in Science & Technology 1(2):27-32
mg/day citalopram. Ther. Drug Monit. 25:600- pharmacokinetics of citalopram. Reviews in Lima, C.A.M., Baumann, P., Amey, M.B., Brogli, C., Jacquet, S., Cochard, N., Golay, K.P., Eap, C. pharmacokinetics of citalopram and other SSRIs. 2005. Effect of age and gender on citalopram and Int. Clin. Psychopharmacol. 11(Suppl 1):5-11. Bezchlibnyk-Butler, K., Aleksic, I., Kennedy, S.H. concentrations in adults and elderly depressed 2000. Citalopram – a review of pharmacological patients. Prog. Neuropsychopharmacol. Biol. and clinical effects. J. Psychiatry. Neurosci. Milne, R.J., and Goa, K.L. 1991. Citalopram. A Dahl, M.L., and Sjoqvist, F. 2000. Pharmacogenetic monitoring of antidepressants and neuroleptics. potential in depressive illness. Drugs. 41(3):450- Foglia, J.P., Pollock, B.G., Kirshner, M.A., Rosen, J., Noble, S., and Benfield, P. 1997. Citalopram: A review of its pharmacology, clinical efficacy and citalopram enantiomers and metabolites in elderly tolerability in the treatment of depression. CNS patients. 1997. Psychopharmacol. Bullet. 33:109- Ohlsson, R.S., Mwinyi, J., Andersson M., Baldwin, R.M., Pedersen, R.S., Sim, S.C., Bertilsson, L., Pharmacokinetic comparison of oral solution and Ingelman-Sundberg, M., Eliasson, E. 2008. tablet formulations of citalopram: A single-dose, Kinetics of omeprazole and escitalopram in relation to the CYP2C19*17 allele in healthy subjects. Eur. J. Clin. Pharmacol. 64(12):1175- Hiemke, C. and Hartter, S. 2000. Pharmacokinetics of Owens, M.J., Knight D.L., Nemeroff, C.B. 2001. Hiemke, C. 20008a. Clinical utility of drug transpoter binding profile of escitalopram and R – measurement and pharmacokinetics: therapeutic fluoxetine. Biol. Psychiatry. 50: 345-350. drug monitoring in psychiatry. Eur. J. Clin. Pollock, B.G. (2001). Citalopram: a comprehensive review. Expert opin pharmacother. 2(4): 681-698. Hiemke, C. 2008b. Individualized treatment with Reis, M., Olsson, G., Carlsson, B., Lundmark, J., tricyclic antidepressives. The pharmacogenetics Dahl, M.L., Walinder, J., Ahlner J., Bengtsson, F. of depression. Pharm. Unserer. Zeit. 37(3):234- 2002. Serum Levels of Citalopram and Its Main Metabolites in Adolescent Patients Treated in a Hiemke, C. 2008c. Therapeutic drug monitoring in neuropsychopharmacology: does it hold its promises? Eur. Arch. Psychiatry. Clin. Neurosci. Reis, M., Lundmark, J., Bengtsson, F. 2003. Citalopram: A 5-Year Experience in Sweden, 1992–1997. Ther. Drug Monit. 25(2):183-191. Reis, M., Aamo, T., Spigset, O., Ahlmer, J. 2009. Serum Concentrations of Antidepressant Drugs in Joffe, P., Larsen, F.S., Pedersen, V., Ring-Larsen, H., a Naturalistic Setting: Compilation Based on a Aaes-Jorgensen, T., Sidhu, J. 1998. Single-dose Large Therapeutic Drug Monitoring Database. pharmacokinetics of citalopram in patients with moderate renal insufficiency or hepatic cirrhosis Rudberg, I., Mohebi, B., Hermann, M., Refsum, H., compared with healthy subjects. Eur. J. Clin. Molden, E. 2008a. Impact of the ultrarapid CYP2C19*17 allele on serum concentration of Joubert, A.F. and Stein, D.J. 1999. Citalopram and anxiety disorders. Review in contemporary Rudberg, I., Hermann, M., Refsum, H., Molden, E. Le bloc’h, Y., Woggon, B., Weissenrieder, H., 2008b. Serum concentrations of sertraline and N- Zullıno, D., Brawand-Amey, M., Spagnolı, J., desmethyl sertraline in relation to CYP2C19 Eap, C.B., Baumann, P. 2003. Routine therapeutic genotype in psychiatric patients. Eur. J. Clin. drug monitoring in patients treated with 10–360 New Horizons in Science & Technology 1(2):27-32
Sim, S.C., Risinger, C., Dahl, M.L., Aklillu, E., Christensen, M., Bertilsson, L., Ingelman-Sundberg M. 2006. A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin. Pharmacol. Ther. 79(1):103-113. Unceta, N., Goicolea, M.A., Barrio, R.J. 2011. Analytical procedures for the determination of the selective antidepressant citalopram and its metabolites. Biomed. Chromatogr. 25(1-2):238-257. Wang, G., Lei, H.P., Li, Z., Tan, Z.R., Guo, D., Fan, L., Chen, Y., Hu, D.L., Wang, D., Zhou, H.H. 2009. The CYP2C19 ultra-rapid metabolizer genotype influences the pharmacokinetics of voriconazole in healthy male volunteers. Eur. J. Clin. Pharmacol. 65(3):281-285. Yin, O.Q., Wing, Y.K., Cheung, Y., Wang, Z.J., Lam, S.L., Chiu, H.F., Chow, M.S. 2006. Phenotype-genotype relationship and clinical effects of citalopram in Chinese patients. J. Clin. Psychopharmacol. 26(4):367-372. Yu, B.N., Chen, G.L., He, N., Ouyang, D.S., Chen, Pharmacokinetics of citalopram in relation to genetic polymorphism of CYP2C19. Drug Metab. Dispos. 31(10):1255-1259.



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