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Biomedical subjects

J T Biggs

Publications and source records attributed to J T Biggs.

At least 55 records · Page 3Linked to original sources

Contribution to the pharmacokinetics of amitriptyline.

The clinical pharmacokinetics of amitriptyline were studied in four volunteers after the oral administration of 75 mg. Peak amitriptyline plasma concentrations ranged from 10.8 to 43.7 ng/ml. The disappearance was biphasic and followed first-order kinetics. The mean elimination half-life was 36.1 hours. The mean estimated first-pass metabolism of amitriptyline was 60 per cent. Significant quantities of the metabolite, nortriptyline, were produced although peak concentrations ranged from only 5.9 to 12.3 ng/ml. The relationship between these findings to clinical practice and earlier reports is discussed.

Adult↗

Intrapatient variability of serial steady-state plasma tricyclic antidepressant concentrations.

Nine or 10 serial steady-state plasma measurements of amitryptyline, desipramine, desmethyldoxepin, doxepin, imipramine, nortriptyline, or protriptyline were made in 23 depressed patients. Each patient was monitored for compliance by pill counts, and sampling time was controlled carefully to determine intrapatient variability of steady-state tricyclic levels on a day-to-day basis. The coefficients of variation during serial sampling of the various ingested drugs were: amitriptyline, 21%; desipramine, 26%; doxepin, 21%; imipramine, 14%; nortriptyline, 13%; and protriptyline, 17%. The therapeutic ranges for the tricyclic antidepressants are relatively wide, so coefficients of variation of these magnitudes indicate that the position of an individual patient in relation to the optimal therapeutic range can be reliably determined on a clinical basis.

Antidepressive Agents, Tricyclic↗

Clinical pharmacology and toxicology of antidepressants.

Described as the drugs of choice in treating acute depression, the tricyclics are unusual in that too high a dosage may be as ineffective as one that is too low, and plasma levels may vary as much as 30-fold among patients given the same dosage. After the recommended approach to determining appropriate dosage has been tried, the 15% or so of patients who do not respond are not likely to benefit from a switch of drugs.

Antidepressive Agents, Tricyclic↗

Validity of the Zung Self-rating Depression Scale.

The Zung Self-rating Depression Scale (ZSDS) correlated well (0.69) with the treating physician's global rating in 26 depressed out-patients during the six weeks of treatment with a tricyclic anti-depressant. In a larger sample of 41 patients, a high correlation was found between the ZSDS and the Hamilton Rating Scale. The sensitivity of the ZSDS was found to be adequate. The scale was able to differentiate, at the 0.05 level, four severity groups classified on the basis of the global rating. The importance of the direct relationship between the range of severity studied and the value of the correlation coefficient was discussed. Previous investigations and the results of this study indicate that the ZSDS is a valid and sensitive measure of clinical severity in depressed patients and support its continued use as a research instrument.

Adult↗

A rating scale for mania: reliability, validity and sensitivity.

An eleven item clinician-administered Mania Rating Scale (MRS) is introduced, and its reliability, validity and sensitivity are examined. There was a high correlation between the scores of two independent clinicians on both the total score (0.93) and the individual item scores (0.66 to 0.92). The MRS score correlated highly with an independent global rating, and with scores of two other mania rating scales administered concurrently. The score also correlated with the number of days of subsequent stay in hospital. It was able to differentiate statistically patients before and after two weeks of treatment and to distinguish levels of severity based on the global rating.

Bipolar Disorder↗

Imipramine and desipramine plasma levels: relationship to dosage schedule and sampling time.

Tricyclic antidepressant plasma levels were determined after administration if imipramine (11 patients) and desipramine (ten patients) as a single daily bedtime dose or in divided doses. Plasma levels of the tricyclics were relatively stable on both dosage schedules due to the long plasma half-lives of these drugs. No difference was found between the two dosage schedules and the therapeutic effectiveness or the severity of side effects. The majority of patients preferred the single dose schedule. These findings support the use of a single daily dose of imipramine and desipramine.

Adult↗

Dosage schedule and plasma levels of doxepin and desmethyldoxepin.

Plasma levels of doxepin and its metabolite desmethyldoxepin were determined in 7 depressed patients treated with doxepin hydrochloride in 3 divided doses at 1000, 1600, and 2200 hours (t.i.d.), and repeated after changing the dosage schedule to a single daily bedtime (h.s.) dose at 2200 hours. Doxepin and its metabolite were measured at 9000, 1200, 1500, and 1800 hours. None of the individual patients showed clinically significant changes in their plasma concentration of tricyclic antidepressant on the 2 dosage schedules. No difference in the clinical condition of the patients was detected on the 2 dosage schedules using the Zung Self Rating Depression Scale, however patients experienced more morning sedation while on the single h.s. dosage. This study provides pharmacological support for the prescription of doxepin on a once daily basis.

Adult↗

Tricyclic plasma levels. Effect of age, race, sex, and smoking.

Steady-state plasma tricyclic antidepressant levels were determined in 65 patients undergoing treatment for depression with either amitriptyline hydrochloride or nortriptyline hydrochloride to determine if common factors such as age, race, sex, or smoking status were predictors of steady-state drug levels that have been shown to vary up to 36-fold. Evaluation of these factors did not disclose differences in the rate of demethylation of amitriptyline to nortriptyline, or steady-state tricyclic levels in the amitriptyline-treated patients. No differences were found in the nortriptyline-treated patients except regarding race. Black patients had significantly higher (50%) nortriptyline plasma levels than did white patients, which may explain the more rapid response to tricyclic treatment demonstrated in blacks. Decreased rates of nortriptyline metabolism in blacks can result in increased side effects and treatment failure if the therapeutic plasma range is exceeded.

Amitriptyline↗

Tricyclic antidepressant overdose: incidence of symptoms.

Forty consecutively hospitalized patients who had overdosed primarily with a tricyclic antidepressant (TCA) were observed until discharge. The severity of the overdose was documented by serial measurements of plasma TCA levels. Nineteen of the patients became comatose, 16 required supportive respiration, and 2 died. Individual symptoms in the 13 patients having plasma TCA levels greater than 1,000 ng/ml are shown. Plasma TCA measurements more reliably define patients who are at risk for major medical complications following overdose than does the amount of drug ingested by history. In the absence of plasma measurements, a QRS duration of 100 msec or more on a routine ECG within the first 24 hours defined all patients with major TCA overdoses.

Amitriptyline↗