Serum levels of olanzapine and its N-desmethyl and 2-hydroxymethyl metabolites in child and adolescent psychiatric disorders: effects of dose, diagnosis, age, sex, smoking, and comedication.


:The aim of this study was to assess dose-related steady-state serum concentrations of olanzapine (OLZ) and its metabolites N-desmethyl OLZ (DMO) and 2-hydroxymethyl OLZ (2-OH-OLZ) (assessed by high-performance liquid chromatography) in 122 child and adolescent psychiatric patients (age 16.9 +/- 2.2, range, 10-21 years; 74 males, 48 females) with a variety of diagnoses: schizophrenia group (n = 80); nonschizophrenia group (n = 29); anorexia nervosa (AN) group (n = 13). Median OLZ serum concentrations were 32.7 (range, 1-118; all patients), 37.7 (2-115; schizophrenia group), and 18.7 (1-63, AN group) ng/mL. The median OLZ concentration-to-dose (C/D) ratio (n = 122) was 2.6, with 90% of the distribution between 0.8 and 5.5 (ng/mL)/(mg/d). OLZ concentration was significantly correlated with DMO (r = 0.567; P < 0.0005) but not with 2-OH-OLZ (r = 0.122; P = 0.188). Daily OLZ dose was correlated with OLZ concentration in all (r = 0.684; P < 0.0005), schizophrenic (r = 0.542; P < 0.0005), and AN (r = 0.805; P = 0.001) patients, respectively. Patients aged less than 16 years displayed similar C/D for OLZ (P = 0.58) but higher C/D for DMO (P = 0.003) than those 16 years or older. AN patients received lower median OLZ doses (7.5; 5-15 mg) than schizophrenic patients (12.5; 2.5-40 mg), even after correcting for body mass index (P = 0.02). OLZ dose did not differ (P = 0.088) between smokers and nonsmokers, but smokers showed lower C/D for OLZ than nonsmokers (P = 0.008). C/D for OLZ was 38% higher (P = 0.041) under comedication with selective serotonin reuptake inhibitors when compared with OLZ monotherapy. Multiple linear regression analysis revealed that 46% of the variation of OLZ concentration can be explained by dose, diagnosis, age, sex, smoking, and comedication. The data are compared with the literature, and the relevance of therapeutic antipsychotic drug monitoring in previously sparsely investigated subgroups, such as children and adolescents or patients with AN, is emphasized.


Ther Drug Monit


Theisen FM,Haberhausen M,Schulz E,Fleischhaker C,Clement HW,Heinzel-Gutenbrunner M,Remschmidt H




Has Abstract


2006-12-01 00:00:00














  • Saliva as a valid alternative to serum in monitoring intravenous caffeine treatment for apnea of prematurity.

    abstract::Caffeine is a potentially useful alternative to theophylline for the treatment and prevention of apnea of prematurity because of its lower toxicity and longer terminal half-life. Monitoring of salivary caffeine concentrations is less invasive than blood sampling, especially in very sick premature neonates. Caffeine ci...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Lee TC,Charles BG,Steer PA,Flenady VJ

    更新日期:1996-06-01 00:00:00

  • Factors associated with long-term renal allograft survival.

    abstract::Major advances in immunosuppression and reductions in the rates of acute rejection have led to increasing graft and patient survival rates during the past two decades. Chronic dysfunction of the renal allograft, however, remains a major clinical problem and probably represents the end result of the complex interplay b...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,评审


    authors: Kaplan B,Srinivas TR,Meier-Kriesche HU

    更新日期:2002-02-01 00:00:00

  • Δ9-Tetrahydrocannabinol and Cannabidiol Time Courses in the Sera of "Light Cannabis" Smokers: Discriminating Light Cannabis Use from Illegal and Medical Cannabis Use.

    abstract:BACKGROUND:Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) time courses in serum and physiological and behavioral effects associated with smoking 1 or 4 "light cannabis" cigarettes were studied. Biomarkers to differentiate light cannabis versus illegal and medical cannabis use were also investigated. METHODS:Sera ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Pichini S,Mannocchi G,Berretta P,Zaami S,Pirani F,Pacifici R,Busardò FP

    更新日期:2020-02-01 00:00:00

  • Identification of uridine diphosphate glucuronosyltransferases involved in the metabolism and clearance of mycophenolic acid.

    abstract::Mycophenolic acid, the active metabolite of the immunosuppressant and antiproliferative agent, mycophenolate mofetil, is primarily metabolized by glucuronidation to the inactive 7-O-glucuronide. Although the uridine diphosphate (UDP) 7-O-glucuronide is the principal excretion product of this drug, carboxyl-linked gluc...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,评审


    authors: Mackenzie PI

    更新日期:2000-02-01 00:00:00

  • Interlaboratory variability in drug assay: a comparison of quality control data with reanalysis of routine patient samples. I: Anticonvulsant drugs and theophylline. Clinical Pharmacology and Toxicology Study Group, Italian Society for Clinical Biochemist

    abstract::The interlaboratory variability in the assay of theophylline and various anticonvulsant drugs was evaluated in a 16-month prospective study by using two independent experimental approaches: (a) a conventional method based on the distribution of quality control (QC) lyophilized human sera spiked with the test drugs (ph...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章



    更新日期:1991-03-01 00:00:00

  • A New Enzyme-Linked Immunosorbent Assay for a Total Anti-T Lymphocyte Globulin Determination: Development, Analytical Validation, and Clinical Applications.

    abstract:BACKGROUND:Anti-T lymphocyte globulin (ATLG) modulates the alloreactivity of T lymphocytes, reducing the risk of immunological posttransplant complications, in particular rejection and graft-versus-host disease, after allogeneic hematopoietic stem cell transplantation (HSCT). We developed and validated a new enzyme-lin...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Montagna M,La Nasa G,Bernardo ME,Piras E,Avanzini MA,Regazzi M,Locatelli F

    更新日期:2017-06-01 00:00:00

  • A simple fluorescence high-performance liquid chromatographic assay for dihydroquinidine in serum.

    abstract::A simple and rapid reversed-phase C-18 high-performance liquid chromatography (HPLC) assay without a prior extraction step for dihydroquinidine (HQD) in serum is described. The method is selective and useful for monitoring HQD and its presumed metabolites, quinidine (QD), N-oxide QD, 3-hydroxy QD (3-OHQD), and 10-11-d...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Camsonne R,Moulin MA,Albessard F,Perault M

    更新日期:1984-01-01 00:00:00

  • Generic Olanzapine Substitution in Patients With Schizophrenia: Assessment of Serum Concentrations and Therapeutic Response After Switching.

    abstract:BACKGROUND:Several reports of loss of efficacy or adverse effects have been described after generic substitution of antipsychotics. To date, studies comparing serum drug levels in patients switched to generic antipsychotics in a standard clinical setting are lacking. The aim of this study was to investigate if switchin...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Italiano D,Bruno A,Santoro V,Lanza G,Muscatello MR,Zoccali R,Spina E

    更新日期:2015-12-01 00:00:00

  • Evaluation of limited sampling strategies for estimation of 12-hour mycophenolic acid area under the plasma concentration-time curve in adult renal transplant patients.

    abstract::Mycophenolate mofetil, the oral prodrug of mycophenolic acid, is indicated as immunosuppressive therapy after renal transplantation. To aid in the investigation of pharmacokinetic-pharmacodynamic relationships of mycophenolic acid in the clinical setting, limited blood sampling strategies have been proposed, and model...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Willis C,Taylor PJ,Salm P,Tett SE,Pillans PI

    更新日期:2000-10-01 00:00:00

  • Determination of cefsulodin in biological fluids by high-pressure liquid chromatography.

    abstract::Cefsulodin is a third-generation cephalosporin with a unique specificity for Pseudomonas aeruginosa. To study the pharmacokinetics of this agent in children, a rapid and sensitive high-performance liquid chromatographic micromethod was developed for plasma and urine. Protein was precipitated from plasma with one volum...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Ackers IM,Myers CM,Blumer JL

    更新日期:1984-01-01 00:00:00

  • Validated LC-MS/MS Method for the Simultaneous Determination of Amlodipine and Its Major Metabolites in Human Plasma of Hypertensive Patients.

    abstract:BACKGROUND:No information on the pharmacokinetic characteristics of amlodipine (AML) metabolites is available. This study aimed to develop a method based on isocratic liquid chromatography coupled to tandem mass spectrometry for the simultaneous determination of AML and its 2 major metabolites, dehydroamlodipine (DH-AM...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Taguchi R,Naito T,Sato H,Kawakami J

    更新日期:2017-12-01 00:00:00

  • Possible interaction between acyclovir and antiepileptic treatment.

    abstract::We report a clinically relevant suspected interaction between acyclovir and the antiepileptic drugs phenytoin (PHT) and valproic acid (VPA). In a child receiving PHT and VPA therapy, a 6-day acyclovir treatment reduced PHT and VPA plasma concentrations to subtherapeutic values. This probably worsened both clinical sta...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Parmeggiani A,Riva R,Posar A,Rossi PG

    更新日期:1995-06-01 00:00:00

  • Digoxin and Phenytoin analyses as part of consultations in clinical pharmacology: a study on the use of drugs.

    abstract::The clinical use of digoxin and phenytoin analyses (in 405 and 152 patients, respectively) furnished by our clinical pharmacological laboratory during a five-month period was evaluated prospectively from request forms. Of first-time analyses of digoxin, 12, 38, and 50% fell above, within, and below our recommended ran...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Bergman U,Rane A,Sjöqvist F,Wiholm BE

    更新日期:1981-01-01 00:00:00

  • Individualized dosing of enoxaparin for subjects with renal impairment is superior to conventional dosing at achieving therapeutic concentrations.

    abstract:INTRODUCTION:Enoxaparin is an anticoagulant used in the treatment of thromboembolic diseases. It is a hydrophilic molecule that is, predominantly, eliminated renally with few data to support dosing for subjects with renal impairment and/or obesity. A recently conducted randomized controlled clinical trial compared indi...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,随机对照试验


    authors: Barras MA,Duffull SB,Atherton JJ,Green B

    更新日期:2010-08-01 00:00:00

  • The evolution of therapeutic immunosuppression and the potential impact of drug concentration monitoring.

    abstract::The major goal of immunosuppressive development is improved selectivity of the drug's inhibitory action against T and B cell-mediated as opposed to nonspecific granulocyte-, monocyte-, and macrophage-mediated resistance. This enterprise demands increased knowledge of alloantigen-induced stimulation, signal transductio...

    journal_title:Therapeutic drug monitoring

    pub_type: 历史文章,杂志文章


    authors: Kahan BD

    更新日期:1995-12-01 00:00:00

  • High-performance liquid chromatography of clomipramine and metabolites in human plasma and urine.

    abstract::An isocratic, high-performance liquid chromatography method has been developed for simultaneous determination of the tricyclic antidepressant clomipramine and six metabolites: desmethylclomipramine, 2- and 8-hydroxy-clomipramine, 2- and 8-hydroxydesmethylclomipramine and didesmethyl-clomipramine in plasma and urine. I...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Nielsen KK,Brøsen K

    更新日期:1993-04-01 00:00:00

  • Pharmacokinetic Variability and Clinical Use of Lacosamide in Children and Adolescents in Denmark and Norway.

    abstract:BACKGROUND:The indication for the antiepileptic drug lacosamide (LCM) was recently extended to include children from the age of 4 years. Real-life data on the use and serum concentrations of LCM in children and adolescents are limited. The purpose of this study was to investigate the use of LCM in this patient group in...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Larsen Burns M,Nikanorova M,Baftiu A,Borg Rasmussen J,Johannessen SI,Johannessen Landmark C

    更新日期:2019-06-01 00:00:00

  • A comparison of venous versus capillary measurements of drug concentration.

    abstract::Accessing patient's veins for drug level sampling is not always feasible. The use of capillary sampling techniques is often utilized when venous access is hampered. In the therapeutic monitoring of patients, unexpected drug level results often occur that can be caused by a number of different factors. The possibility ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Murphy JE,Peltier T,Anderson D,Ward ES

    更新日期:1990-05-01 00:00:00

  • Clinical implications of thiopurine methyltransferase--optimization of drug dosage and potential drug interactions.

    abstract::Thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme that preferentially catalyzes the S-methylation of aromatic and heterocyclic sulphydryl compounds, such as the thiopurine drugs azathioprine, mercaptopurine, and thioguanine. These drugs form the same terminal metabolites, the thioguanine nucleotides (TGNs). ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,评审


    authors: Lennard L

    更新日期:1998-10-01 00:00:00

  • Quantification of Delta9-tetrahydrocannabinol and its major metabolites in meconium by gas chromatographic-mass spectrometric assay: assay validation and preliminary results of the "meconium project".

    abstract::A rapid and simple procedure based on gas chromatography-mass spectrometry (GC-MS) is described for determination of Delta-tetrahydrocannabinol (THC), 11-hydroxy-Delta-tetrahydrocannabinol (THC-OH) and 11-nor-Delta-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in meconium using Delta-tetrahydrocannabinol (Delta-TH...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Marchei E,Pellegrini M,Pacifici R,Palmi I,Lozano J,García-Algar O,Pichini S

    更新日期:2006-10-01 00:00:00

  • Valproic acid binding to human serum and human placenta in vitro.

    abstract::The binding characteristics of the antiepileptic agent and teratogen valproic acid for human serum and human placenta were investigated utilizing equilibrium dialysis of the drugs in serum and in homogenates of whole placenta so that the transplacental transfer of the drug could be better defined. A low-capacity, high...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Bailey DN,Briggs JR

    更新日期:2005-06-01 00:00:00

  • Oral aripiprazole-induced severe hypoglycemia.

    abstract::This case report highlights a very rare adverse drug reaction caused by oral aripiprazole resulting in severe hypoglycemia. A 72-year-old-male patient suffering from Parkinson disease on prolonged carbidopa plus levodopa combination therapy (carbidopa 25 mg plus levodopa 100 mg, thrice daily) for 1.3 years was recentl...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,评审


    authors: Mondal S,Saha I,Das S,Ganguly A,Ghosh A,Kumar Das A

    更新日期:2012-06-01 00:00:00

  • Cyclosporin A trough levels correlate with serum lipoproteins and apolipoproteins: implications for therapeutic drug monitoring of cyclosporin A.

    abstract::In a prospective study over 6 months, the relationship between serum lipid parameters and CsA whole blood trough concentrations was investigated in 39 renal transplant recipients receiving a triple immunosuppressive therapy with cyclosporin (CsA), azathioprine and prednisone. CsA trough concentrations were measured wi...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: von Ahsen N,Helmhold M,Schütz E,Eisenhauer T,Armstrong VW,Oellerich M

    更新日期:1997-04-01 00:00:00

  • Effects of carbamazepine coadministration on plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine.

    abstract::Effects of carbamazepine coadministration on plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP) were studied in six depressed patients treated with trazodone. The daily dose of trazodone was 150 mg in three cases and 300 mg in three cases. Carbamazepine, 400 mg/day, was coad...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Otani K,Ishida M,Kaneko S,Mihara K,Ohkubo T,Osanai T,Sugawara K

    更新日期:1996-04-01 00:00:00

  • Monitoring of plasma methadone: intercorrelation between immunoassay and gas chromatography-mass spectrometry.

    abstract::Determination of plasma methadone is essential in connection with dose adjustments for patients participating in methadone maintenance programs. We successfully adapted the existing fluorescence polarization immunoassay (FPIA) kit intended for urinary methadone to plasma assays. A concentration interval of 50-900 ng/m...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Beck O,Boreus LO,Borg S,Jacobsson G,Lafolie P,Stensiö M

    更新日期:1990-09-01 00:00:00

  • Impact of POR and CYP3A5 Polymorphisms on Trough Concentration to Dose Ratio of Tacrolimus in the Early Post-operative Period Following Kidney Transplantation.

    abstract:BACKGROUND:Tacrolimus, a critical dose drug, is widely used in transplantation. Knowing the contribution of genetic factors, which significantly influence tacrolimus variability, is beneficial in the personalization of its starting dose. The significant impact of CYP3A5*3 polymorphisms on tacrolimus exposure has been r...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章


    authors: Phupradit A,Vadcharavivad S,Ingsathit A,Kantachuvesiri S,Areepium N,Sra-Ium S,Auamnoy T,Sukasem C,Sumethkul V,Kitiyakara C

    更新日期:2018-10-01 00:00:00

  • Drugs in sports: analytical trends.

    abstract::A minority of athletes continues to use prohibited drugs in sports to enhance performance. Athletes discovered using these drugs can be subject to severe penalties, often resulting in media and public scrutiny, especially at major events such as the Olympic Games. The International Olympic Committee (IOC) has set out ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,评审


    authors: Kazlauskas R,Trout G

    更新日期:2000-02-01 00:00:00

  • A novel system for the determination of antidepressant concentrations in human breast milk.

    abstract::The high incidence of psychiatric illness in the postpartum period and the increasing percentage of women who breastfeed has focused attention on the treatment of breastfeeding women with psychotropic medications and, additionally, the exposure of nursing infants to these medications. Consequently, there has been an i...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Hostetter AL,Stowe ZN,Cox M,Ritchie JC

    更新日期:2004-02-01 00:00:00

  • Ultra fast liquid chromatography-tandem mass spectrometry routine method for simultaneous determination of cyclosporin A, tacrolimus, sirolimus, and everolimus in whole blood using deuterated internal standards for cyclosporin A and everolimus.

    abstract::Specific chromatographic methods for the measurement of cyclosporin A, tacrolimus, sirolimus, and everolimus blood levels in patients with organ transplants are time consuming when large numbers of samples must be processed. The authors developed a robust and fast (1 minute) online solid-phase extraction liquid chroma...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Meinitzer A,Gartner G,Pilz S,Stettin M

    更新日期:2010-02-01 00:00:00

  • A population pharmacokinetic-metabolism model for individualizing ciprofloxacin therapy in ophthalmology.

    abstract::The purpose of this study was to construct a population pharmacokinetic (PK) metabolism (MB) model to describe ciprofloxacin (C) concentrations in plasma and vitreous and aqueous humors in 26 patients. Ciprofloxacin was given as a 3-day oral prophylactic treatment to 26 patients before vitrectomy. Plasma, vitreous, an...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章


    authors: Di Marco MP,Chen J,Wainer IW,Ducharme MP

    更新日期:2004-08-01 00:00:00