title: Extreme values of the concentration/dose ratio as a risk factor of obtaining suboptimal nortriptyline serum concentrations.
abstract: Using nortriptyline as an example of a typical tricyclic antidepressant, I studied the relation between the steady-state concentration/dose ratio (C/D) and the performance of therapeutic drug monitoring (TDM), with a focus on the frequency of serum concentrations located in the therapeutic interval. A TDM database comprising 1,214 patients, of whom 619 patients had more than one sample taken, was used. The median C/D value for the patients was 4.05 [nM]/mg with 5th and 95th percentiles of 1.80 and 9.60, respectively. A total of 18.6% of the patients with C/D values below the 5th percentile had serum concentrations in the therapeutic interval at the first occasion, increasing to 49% for the average of the succeeding samples. These values were lower than those for the total group, 60.4 and 68.9%, respectively. For those with C/D values exceeding the 95th percentile, 36.2% had initial serum concentrations in the therapeutic interval, increasing to 66.3% for the average of succeeding samples. Only 11 patients (0.9%) had very high initial serum concentrations (> 1,200 nM). Thus patients with low C/D values are at risk of being underdosed, even after successive samples, whereas adequate dose correction is more likely to be implemented for those with average or high C/D values. Saturation kinetics for those with low C/D values was not a problem of clinical significance. Neither was lack of steady-state at the first occasion a problem for those with high C/D values (suspected poor metabolizers).
authors.affiliation: Institute for Basic Research in Psychiatry, Psychiatric Hospital in Aarhus, Risskov, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Linnet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects* / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009661:Nortriptyline / Q000009:adverse effects* / Q000097:blood* / Q000493:pharmacokinetics; D012307:Risk Factors
chemical_list: D000929:Antidepressive Agents, Tricyclic; D009661:Nortriptyline