Amitriptyline Dosage Prediction in Elderly Patients from Plasma Concentration at 24 Hours after a Single 100mg Dose

Abstract

Fifteen depressed elderly patients (14 female, 1 male; mean age 85 years) received a single oral dose of amitriptyline. The concentration of amitriptyline plus nortriptyline in a blood sample taken 24 hours later was used to predict by means of a nomogram the amitriptyline dosage required for each patient. Each dose was selected to produce steady-state amitriptyline plus nortriptyline concentrations close to 140 micrograms/L. The daily dosage ranged from 20 to 100mg (mean 62mg). Patients received the individually calculated dose each night, and weekly blood samples were obtained for drug analysis. At 2 weeks, mean amitriptyline plus nortriptyline concentrations were 118 +/- 21 micrograms/L. Eight of the patients were studied for a further 2 weeks and the mean amitriptyline plus nortriptyline concentration was then 111 +/- 19 micrograms/L. The dose prediction test is easy to use and ensures each patient receives an adequate but safer dose of amitriptyline than might otherwise be prescribed routinely.

Discrepancies Between Pharmacokinetic Studies of Amitriptyline

“…Recently, Dawling et al (1984) have demonstrated that a nomogram can be used in elderly depressed patients to predict the dose of amitriptyline necessary to achieve a selected concentration of amitriptyline plus nortriptyline. From our study (Schulz et aI., 1983b) in subjects wh6 received single oral doses of amitriptyline, the normalised concentrations of amitriptyline at 12, 24 a~d 36 hours after the single oral dose were very dependent on the CLo uncorrected for bodyweight (r = 0.88, 0.93 and 0.85 for the 12-, 24-and 48-hour samples, respectively).…”

Plasma Concentrations of Mianserin after Single Dose and at Steady-State in Depressed Elderly Patients

“…However, this relationship is obviously more complex than one which can be represented by a log-linear equation as the linear least-squares regression correlation coefficients were not significantly improved by logarithmic transformation of the data. In our previous studies with elderly depressed patients a relationship was demonstrated between concentrations of nortriptyline obtained at 24 hours after a single dose and those obtained at steadystate (Dawling et al 1981(Dawling et al , 1984. The relationships were linear and allowed construction of drug dosage nomograms for amitriptyline or nortriptyline therapy.…”

“…For this reason we previously investigated the relationship between the metabolism of single and multiple doses of both amitriptyline and nortriptyline in elderly patients; there was a good relationship for each drug between concentrations obtained at 24 hours following a single test dose and those at steady-state. This allowed use of the single-dose concentration for prediction of individual dose requirements to achieve steady-state concentrations within a predetermined range (Dawling et al 1981(Dawling et al , 1984. Other investigators have obtained similar results in younger populations using imipramine and desipramine (Brunswick et al 1979;Potter et al 1980).…”

Desipramine Dose Prediction Based on 24-Hour Single-Dose Levels: Feasibility and Validity

“…An early single drug level could therefore be used to predict the dosage needed to produce a therapeutic level. When the authors started their work, this method ofrapid dose adjustment had only been prospectively applied and reported for amitriptyline (Dawling et al, 1984;Levyet al, 1982). Since then, Nelson et al (1987) have published a study for desipramine.…”

“…Außerdem erhielten 11 von 19 Patienten seit dem 3. Behandlungstag eine Tagesdosis von 250 mg oder mehr Desipramin; bei 10 dieser Patienten war die Dosierung den jeweiligen Erfordernissen angepaßt.When the authors started their work, this method ofrapid dose adjustment had only been prospectively applied and reported for amitriptyline (Dawling et al, 1984; Levyet al, 1982). Since then, Nelson et al (1987) have published a study for desipramine.…”