Radioimmunoassay of Salivary Digoxin by Simple Adaptation of a Kit Method for Serum Digoxin

Mahmod, S.M.; Ds, Smith; Landon, J.

doi:10.1097/00007691-198703000-00016

Cited by 10 publications

(6 citation statements)

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“…The saliva/serum concentration ratio of digoxin (CSSA/CS) was 0.69 after a single dose. This value was close to the one reported by Mahmod et al (9), and it decreased to 0.53 in the steady state. The digoxin concentration in the erythrocytes increased in the steady state above the total serum concentration.…”

Section: Resuitssupporting

confidence: 91%

“…Therefore, it should easily diffuse from the blood compartment into saliva, independently of variations in the the pH-gradient. Mahmod et al (9) have pointed out that digoxin appears in saliva at its maximum level within l nainute of intravenous injection. Joubert (12) has observed that contamination can occur and recommended that mixed saliva should be collected just prior to oral administf ation of the next digoxin dosage.…”

Section: Discussionmentioning

confidence: 99%

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Reasons for Intraindividual Inconstancy of the Digoxin Saliva to Serum Concentration Ratio

Haeckel¹,

Mühlenfeld²

1989

Clinical Chemistry and Laboratory Medicine

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Haeckel and Mühlenfeld: Inconstancy of the digoxin saliva to serum ratio 653 Summary: When a constant dose of digoxin was administered orally over several days, the digoxin concentration in saliva and erythrocytes rose faster than in serum. Thus, the saliva/serum concentration ratio was below 1.0 after a single dose and above 1.0 in the steady state.The digoxin concentration was relatively high in "unstimulated" (more or less spontaneous) saliva and decreased with Stimulation of the salivary flow rate. It therefore appeared that the actual salivary digoxin concentration depended on 2 components: the digoxin concentration in "stimulated" saliva depended only on the rapid diffusion from the blood into saliva, and the concentration in the "unstimulated" saliva depended on the rapid diffusion and on a slower exchange with the intracellular compartment. It is suggested that unstimulated saliva reflects the intracellular digoxin concentration and stimulated saliva reflects the free digoxin concentration of the serum.Both effects must be taken in account when interpreting the saliva/serum ratio, and they may explain conflicting results in the literature.

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Section: Resuitssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Reasons for Intraindividual Inconstancy of the Digoxin Saliva to Serum Concentration Ratio

Haeckel¹,

Mühlenfeld²

1989

Clinical Chemistry and Laboratory Medicine

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“…In a study evaluating the efficacy of oral fluid therapeutic drug monitoring of digoxin in children, investigators found no correlation between plasma total or free digoxin levels and oral fluid concentrations, indicating that oral fluid testing is not an acceptable means of monitoring digoxin in this population 108 . In another study digoxin levels in saliva were correlated with plasma levels and with the free fraction in plasma 109 . When a constant dose of digoxin was administered orally over several days, the digoxin concentration in saliva and erythrocytes rose faster than in serum.…”

Section: Saliva Therapeutic Drug Management Applied To Drug Classesmentioning

confidence: 99%

“…108 In another study digoxin levels in saliva were correlated with plasma levels and with the free fraction in plasma. 109 When a constant dose of digoxin was administered orally over several days, the digoxin concentration in saliva and erythrocytes rose faster than in serum. Thus, the S/P ratio was below 1.0 after a single dose and above 1.0 in the steady state.…”

Section: Antiarrhythmicsmentioning

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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“…Several analytical methods, including thin-layer chromatography [2], high performance liquid chromatographic (HPLC) techniques [3 -19], immunoassays [20 -24], and capillary electrophoresis [25], have been reported for the determination of digitalis glycosides in various matrices. The immunoassays are sensitive and convenient; however, the methods would be inappropriate for determination of the cardiac glycosides in the potential presence of degradation or hydrolytic products of the glycosides or impurities [26,27]. Cross reactions are sometimes noted with the immunoassay kits, especially with highly similar chemical structures.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of digoxin and digitoxin by micellar electrokinetic chromatography and application to drug formulations

Tseng

Lin

et al. 2003

J of Separation Science

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A simple micellar electrokinetic chromatographic method is described for simultaneous determination of digoxin and digitoxin. The simultaneous analysis of digoxin and digitoxin was performed in Tris buffer (10 mM; pH 9) with 90 mM sodium dodecyl sulfate and 10% isopropyl alcohol as an anionic surfactant and organic modifier. Under these conditions, good separation with high efficiency is achieved in short analysis times. Several parameters affecting the separation of the drugs were studied, including the pH and concentrations of the Tris buffer and sodium dodecyl sulfate. The linear range of the method for the determination of digoxin and digitoxin was over 0.01 -0.3 mg/mL; the detection limit (signal to noise ratio = 3; injection 3.5 kPa 3 s) was 4 and 6 lg/mL, respectively. Application of the proposed method to the determination of digoxin in commercial tablets and in injections proved to be feasible.

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Radioimmunoassay of Salivary Digoxin by Simple Adaptation of a Kit Method for Serum Digoxin

Cited by 10 publications

References 0 publications

Reasons for Intraindividual Inconstancy of the Digoxin Saliva to Serum Concentration Ratio

Reasons for Intraindividual Inconstancy of the Digoxin Saliva to Serum Concentration Ratio

The Use of Oral Fluid for Therapeutic Drug Management

Simultaneous determination of digoxin and digitoxin by micellar electrokinetic chromatography and application to drug formulations

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