On the Relationship between Free Plasma and Saliva
Amitriptyline and Nortriptyline

Baumann, Pierre; Tinguely, D; Koeb, L.; Schöpf, Josef; Le, Probatova

doi:10.1159/000468569

Cited by 16 publications

(7 citation statements)

References 3 publications

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“…For amitriptyline and nortriptyline, no significant relationship was found between concentrations in saliva and plasma [87]. Many neuropsychiatric drugs are bases, with a pKa value > 9.…”

Section: Oral Fluid For Tdmmentioning

confidence: 88%

“…There is no experimental evidence for the hypothesis, that the assay of unbound ("free") drug concentrations in blood would be advantageous. Moreover, the assay of the free fraction represents an analytical challenge [87]. For imipramine, it has been shown that the drug is rapidly and almost totally cleared by the brain through a single passage in the microvasculature [994].…”

Section: Blood Sample Collectionmentioning

confidence: 99%

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Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Bergemann²,

et al. 2017

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Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.

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“…For amitriptyline and nortriptyline, no significant relationship was found between concentrations in saliva and plasma [87]. Many neuropsychiatric drugs are bases, with a pKa value > 9.…”

Section: Oral Fluid For Tdmmentioning

confidence: 88%

Section: Blood Sample Collectionmentioning

confidence: 99%

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Bergemann²,

et al. 2017

Self Cite

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“…Although amitriptyline and its primary metabolite, nortriptyline, have been detected in oral fluid, research has shown that oral fluid levels poorly reflect concentrations in plasma for tricyclic antidepressant drugs 127 . A single dose of desipramine given to healthy volunteers showed that the S/P ratio of desipramine was time dependent and was much less than unity at 96 h 128 .…”

Section: Saliva Therapeutic Drug Management Applied To Drug Classesmentioning

confidence: 99%

“…126 Although amitriptyline and its primary metabolite, nortriptyline, have been detected in oral fluid, research has shown that oral fluid levels poorly reflect concentrations in plasma for tricyclic antidepressant drugs. 127 A single dose of desipramine given to healthy volunteers showed that the S/P ratio of desipramine was time dependent and was much less than unity at 96 h. 128 A correlation existed, but the variability did not allow prediction of plasma levels from those in saliva. This is in contrast to a better correlation found at steady state and to an apparent decreased variability for ratios in the same individual.…”

Section: Psychoactive Drugsmentioning

confidence: 99%

The Use of Oral Fluid for Therapeutic Drug Management

Langman

2007

Annals of the New York Academy of Sciences

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One of the underlying tenets of clinical pharmacology is that only free drugs are pharmacologically active. It is thought that only free drugs can cross biological membranes to interact with a given receptor to alter its function, and that drug responses, both efficacious and toxic, are a function of unbound concentrations. The rationale for measuring drugs in oral fluid is that the free fraction of a drug in plasma reaches equilibrium with the drug in saliva. Although reports concerning the appearance of organic solutes in saliva have been in the literature for over 70 years, it has only been in the past 30 years that there has been emphasis on the appearance of drugs. Although many assumptions for drug level monitoring in saliva are made, the primary requisite for salivary monitoring to be useful is a constant or predictable relationship between the drug concentration in saliva and the drug concentration in plasma. Measurement of oral fluid drug levels for the purpose of managing patients and making dosage adjustments may be useful for select drugs or drug classes. However, it does not appear to be useful for the majority of drugs therapeutically monitored. Some work with antipsychotic medications has indicated that although the measurement of drug concentrations themselves may not be useful for dosage adjustment, the ratio of parent drug to metabolite may reflect altered metabolic status due to either pharmacogenetic variation or other clinical conditions. Furthermore, analysis of saliva may provide a cost-effective approach for the screening of large populations.

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“…The pKa for the basic drugs amitriptyline, desipramine and nortriptyline is approximately 9.5; thus, changes in salivary pH may potentially affect the Csal/Cup ratio of these drugs (Baumann et al 1982;Cooper et al 1981;DeVane 1986). Baumann et al (1982) examined the relationship between salivary and plasma concentrations (total and free) for the tricyclic antidepressants amitriptyline and nortriptyline.…”

Section: Antidepressantsmentioning

confidence: 99%

Therapeutic Drug Monitoring in Saliva

Drobitch

Svensson

1992

Clinical Pharmacokinetics

179

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This article re-examines the issue of salivary therapeutic drug monitoring (STDM). The anatomy and physiology of saliva and the salivary glands, as well as the effects of disease and drugs on salivary secretion and composition, are discussed briefly. Drugs for which therapeutic drug monitoring (TDM) has been shown useful are individually considered to determine if salivary drug concentrations (Csal) are reflective of plasma free drug concentrations (C(up)). That is, is the Csal/C(up) ratio time- and concentration-independent, as supported by a review of literature data? The primary determinant which appears to govern the potential utility of STDM for many of the drugs is the pKa of the drug. Drugs which are not ionisable or are un-ionised within the salivary pH range (phenytoin, carbamazepine, theophylline) are candidates for STDM based on current literature data. Digoxin and cyclosporin are potential candidates for STDM; however, further studies are necessary to confirm these preliminary findings. On the basis of current literature data, STDM does not appear to be useful for other drugs therapeutically monitored in serum/plasma.

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On the Relationship between Free Plasma and Saliva Amitriptyline and Nortriptyline

Cited by 16 publications

References 3 publications

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

The Use of Oral Fluid for Therapeutic Drug Management

Therapeutic Drug Monitoring in Saliva

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