Lack of Pharmacokinetic Interaction Between Lamotrigine and Olanzapine in Healthy Volunteers

Jann, Michael W.; Hon, Yuen Yi; Shamsi, Shahab A.; Zheng, Jack; Awad, Eric A.; Spratlin, Vicky

doi:10.1592/phco.26.5.627

Cited by 22 publications

(13 citation statements)

References 30 publications

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“…Finally, the developed method was applied to analysis of the plasma samples collected from an LTG-treated subject. The LTG concentrations measured by the CZE-ESI-MS method showed reasonable correlation with the results determined by the HPLC-UV method [15]. In addition, the CZE-ESI-MS demonstrated higher chromatographic efficiency, higher specificity, and fast throughout over the HPLC-UV method.…”

Section: Discussionsupporting

confidence: 59%

“…The sample preparation procedure for plasma was similar to the procedure reported by Shihabi and Oles [16]. The plasma samples were collected over a period of 96 h from a subject after oral administration of 50 mg LTG [15]. Both blank human plasma samples and the subject plasma samples were obtained from Mercer University Southern School of Pharmacy (Atlanta, GA, USA) and stored under 2787C until analysis.…”

Section: Plasma Sample Preparationmentioning

confidence: 99%

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Development of capillary zone electrophoresis‐electrospray ionization‐mass spectrometry for the determination of lamotrigine in human plasma

et al. 2004

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A method of coupling capillary zone electrophoresis (CZE) with electrospray ionization-mass spectrometry (ESI-MS) detection has been developed for monitoring an antiepileptic drug, lamotrigine (LTG) in human plasma. The CZE-MS was developed in three stages: (i) CZE separation and ESI-MS detection of LTG and tyramine (TRM, internal standard) were simultaneously optimized by studying the influence of CZE background electrolyte (BGE) pH, BGE ionic strength, and nebulizer pressure of the MS sprayer; (ii) sheath liquid parameters, such as pH, ionic strength, organic modifier content, and flow rate of the sheath liquid, were systematically varied under optimum CZE-MS conditions developed in the first stage; (iii) MS sprayer chamber parameters (drying gas temperature and drying gas flow rate) were varied for the best MS detection of LTG. The developed assay was finally applied for the determination of LTG in plasma samples. The linear range of LTG in plasma sample assay was between 0.1-5.0 microg/mL with a limit of detection as low as 0.05 microg/mL and run time less than 6 min. Finally, the concentration-time profile of LTG in human plasma sample was found to correlate well when CZE-ESI-MS was compared to a more established method of high-performance liquid chromatography with ultraviolet detection.

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Section: Discussionsupporting

confidence: 59%

Section: Plasma Sample Preparationmentioning

confidence: 99%

Development of capillary zone electrophoresis‐electrospray ionization‐mass spectrometry for the determination of lamotrigine in human plasma

et al. 2004

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“…Moreover, adjunctive lamotrigine, at dosages up to 200 mg/day, did not affect the plasma levels of clozapine, risperidone and their active metabolites, whereas it caused a modest elevation in plasma olanzapine concentration, possibly as a result of inhibition of UGT1A4‐mediated olanzapine glucuronidation, unlikely to be of clinical significance [141]. In this respect, other investigations have reported no modifications in the pharmacokinetics of olanzapine during co‐administration of lamotrigine in healthy volunteers [136,142].…”

Section: Metabolic Drug Interactions Of Newer Antipsychoticsmentioning

confidence: 99%

Metabolic Drug Interactions with Newer Antipsychotics: A Comparative Review

Spina

Leon

2006

Basic Clin Pharma Tox

232

174

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Newer antipsychotics introduced in clinical practice in recent years include clozapine, risperidone, olanzapine, quetiapine, sertindole, ziprasidone, aripiprazole and amisulpride. These agents are subject to drug-drug interactions with other psychotropic agents or with medications used in the treatment of concomitant physical illnesses. Most pharmacokinetic interactions with newer antipsychotics occur at the metabolic level and usually involve changes in the activity of the major drug-metabolizing enzymes involved in their biotransformation, i.e. the cytochrome P450 (CYP) monooxygenases and /or uridine diphosphate-glucuronosyltransferases (UGT). Clozapine is metabolized primarily by CYP1A2, with additional contribution by other CYP isoforms. Risperidone is metabolized primarily by CYP2D6 and, to a lesser extent, CYP3A4. Olanzapine undergoes both direct conjugation and CYP1A2-mediated oxidation. Quetiapine is metabolized by CYP3A4, while sertindole and aripiprazole are metabolized by CYP2D6 and CYP3A4. Ziprasidone pathways include aldehyde oxidase-mediated reduction and CYP3A4-mediated oxidation. Amisulpride is primarily excreted in the urine and undergoes relatively little metabolism. While novel antipsychotics are unlikely to interfere with the elimination of other drugs, co-administration of inhibitors or inducers of the major enzymes responsible for their metabolism may modify their plasma concentrations, leading to potentially significant effects. Most documented metabolic interactions involve antidepressant and anti-epileptic drugs. Of a particular clinical significance is the interaction between fluvoxamine, a potent CYP1A2 inhibitor, and clozapine. Differences in the interaction potential among the novel antipsychotics currently available may be predicted based on their metabolic pathways. The clinical relevance of these interactions should be interpreted in relation to the relative width of their therapeutic index. Avoidance of unnecessary polypharmacy, knowledge of the interaction profiles of individual agents, and careful individualization of dosage based on close evaluation of clinical response and, possibly, plasma drug concentrations are essential to prevent and minimize potentially adverse drug interactions in patients receiving newer antipsychotics.

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“…In one study undertaken in a routine clinical setting, co-administration of lamotrigine with either clozapine, which is primarily metabolized by CYP1A2, or risperidone, which is cleared via CYP2D6 and CYP4A3 enzymes, was seen to have no significant effect on dose-normalized lamotrigine serum levels (Reimers et al, 2005). Similarly, no clinically significant interactions were observed when lamotrigine was co-administered with olanzapine (Jann et al, 2006). Furthermore, aripiprazole does not affect the disposition of co-administered drugs that are primarily metabolized through glucuronidation (e.g., lorazepam).…”

Section: Discussionmentioning

confidence: 97%

A non‐randomized study to investigate the effects of the atypical antipsychotic aripiprazole on the steady‐state pharmacokinetics of lamotrigine in patients with bipolar I disorder

Schieber

Boulton

Balch

et al. 2009

Human Psychopharmacology

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Lack of Pharmacokinetic Interaction Between Lamotrigine and Olanzapine in Healthy Volunteers

Abstract: Lamotrigine and olanzapine can safely be combined in healthy volunteers at the low doses studied, without a clinically significant interaction. When prescribing high doses of olanzapine and lamotrigine for bipolar disorder, patients must be carefully monitored.

Cited by 22 publications

References 30 publications

Development of capillary zone electrophoresis‐electrospray ionization‐mass spectrometry for the determination of lamotrigine in human plasma

Development of capillary zone electrophoresis‐electrospray ionization‐mass spectrometry for the determination of lamotrigine in human plasma

Metabolic Drug Interactions with Newer Antipsychotics: A Comparative Review

A non‐randomized study to investigate the effects of the atypical antipsychotic aripiprazole on the steady‐state pharmacokinetics of lamotrigine in patients with bipolar I disorder

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