PubMed Health⌕ Search

Biomedical subjects

V E Ziegler

Publications and source records attributed to V E Ziegler.

At least 19 recordsLinked to original sources
PubMed1978

Doxepin kinetics.

The kinetics of doxepin (DOX) hydrochloride were studied in 7 volunteers after the oral administration of 75 mg. Peak plasma concentrations of DOX ranged from 8.8 to 45.8 ng/ml and were reached within 4 hr. The disappearance of DOX was biphasic and followed first-order kinetics. The mean DOX half life (t1/2) was 16.8 hr and in individuals ranged from 8.2 to 24.5 hr. The mean apparent volume of distribution was 20.2 L/kg and ranged from 9.1 to 33.3 L/kg. The estimated first-pass metabolism of DOX ranged from 55% to 87% of the oral dose assuming complete absorption. Significant quantities of the metabolite desmethyldoxepin (DMD) were produced. Peak levels of DMD ranged from 4.8 to 14.5 ng/ml and were reached between 2 and 10 hr after administration. The mean t1/2 of DMD was 51.3 hr and in individuals ranged from 33.2 to 80.7 hr. There was no correlation between the DOX and DMD t1/2s. The amount of DMD produced correlated with the plasma concentration of DOX and appears to explain the correlation between the steady-state concentrations of DOX and DMD in patients given DOX.

Adult↗
PubMed1978

Protriptyline kinetics.

The kinetics of protriptyline were examined in 8 subjects after a single oral dose of 30 mg protriptyline hydrochloride. Peak protriptyline levels ranged from 10.4 to 22.3 ng/ml and were reached 6 to 12 hr after the oral dose. The mean protriptyline half-life (t1/2) was 74.3 hr and ranged from 53.6 to 91.7 hr in individual subjects, confirming the long t1/2 of protriptyline reported by Moody and associates. The estimated first-pass metabolism of protriptyline was relatively small, ranging from 10% to 25% of the oral dose, assuming complete absorption. The mean volume of distribution was 22.5 L/kg and ranged from 15.0 to 31.2 L/kg. No relationship was found between the kinetics of protriptyline and those of doxepin studied previously in 7 of the 8 subjects.

Adult↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1977

A comparison study of amitriptyline and nortriptyline with plasma levels.

Forty-one depressed outpatients were treated for six weeks after random assignment to amitriptyline hydrochloride (N = 22) or nortriptyline hydrochloride (N = 19). On a mean daily dose of 119 mg, amitriptyline-treated patients had a mean tricyclic level (amitriptyline plus nortriptyline) of 120 ng/ml. Nortriptyline-treated patients on a mean dose of 117 mg/day had a mean nortriptyline level of 141 ng/ml. The two drugs were equally effective in the treatment of depression. The correlation between the Hamilton Score and the mean tricyclic level was negative in the amitriptyline-treated patients (r = -0.54, P less than .025) and positive in the nortriptyline-treated patients (r = -0.49, P less than .05). Patients treated with amitriptyline or nortriptyline with plasma levels within the therapeutic range, defined in other laboratories, had a better response, as measured by the Hamilton Score (P less than .001), Zung Score (P less than .01), and percent recovered (P less than .001), than those above or below the therapeutic range.

Administration, Oral↗
PubMed1977

Sampling time, dosage schedule, and nortriptyline plasma levels.

Steady-state nortriptyline plasma levels were determined in eight patients at 9 AM, 12 PM, 3 PM, and 6 PM during treatment with nortriptyline hydrochloride administered as a single daily bedtime (hs) dose at 10 PM and repeated after changing the dosage schedule to three times a day (tid) with divided doses at 10 AM, 4 PM, and 10 PM. Overall, the mean levels were stable during the sampling period and comparable on the two schedules. As expected, the plasma level decreased at the later sampling times on the hs schedule and increased on the tid schedule. In seven of the eight patients, the differences on the two dosage schedules were less than 30 ng/ml, which is not considered clinically significant. One patient had a higher plasma nortriptyline level on the tid schedule, which was clinically significant. Standardization of sampling time is of importance when comparing plasma levels and therapeutic response in treatment studies.

Depression↗
PubMed1977

Tricyclic antidepressant plasma levels and adverse effects after overdose.

Forty patients ingesting tricyclic antidepressant (TAD) overdoses were studied as a pharmacologic model to determine whether total tricyclic antidepressant plasma levels correlated with major adverse effects and electrocardiographic findings. Maximum TAD plasma levels were higher in patients who died (p less than 0.025) or had cardiac arrest (p less than 0.02), needed respiratory support (p less than 0.005), were unconscious (p less than 0.02), had grand mal seizures (p less than 0.001), ventricular rate larger than or equal to 120/min (p less than 0.01), cardiac arrhythmia (p less than 0.05), QRS duration larger than or equal to 100 msec (p less than 0.001), or bundle branch block (p less than 0.05). TAD plasma levels correlated with the dose ingested by history (N = 29, r = 0.58, p less than 0.001). Measurement of total TAD (free and protein-bound) appears to correlate well with biologic response.

Antidepressive Agents, Tricyclic↗
PubMed1977

Protriptyline plasma levels and antidepressant response.

Twenty-one depressed outpatients were treated for 4 wk with 20 mg/day of protriptyline. Protriptyline plasma in individuals after 4 wk ranged from 22 ng/ml to 167 ng/ml. There was a negative correlation (-0.50, less than 0.05) between the severity of depression measured by the Hamilton Rating Scale (HRS) and the wk 4 protriptyline concentration. Patients with plasma levels above 70 ng/ml (wk 4) had better outcomes measured by the HRS (p less than 0.05) and the Zung Self-Rating Depression Scale (p less than 0.05) and had greater percent decreases on both scales (p less than 0.05) during treatment than those with lower plasma levels. An upper limit to the therapeutic plasma level range beyond which response to treatment was less satisfactory was not demonstrated in this study.

Adult↗
PubMed1977

Validity of the Hamilton Rating Scale for depression.

In 26 depressed patients, a high correlation (0-89) was found between the Hamilton score and a psychiatrist's global rating and between the change (0-68) in these ratings during treatment. The Hamilton scale was able to differentiate at the o-01 level four degrees of severity based on the global rating. Limiting the range of severity measured was found to lower significantly the correlation between the ratings. A prospective examination of a six-item sub-scale of the Hamilton scale developed by Beck and associates failed to confirm its claimed improvement in sensitivity or validity.

Depression↗