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PubMed2004

A cross-validation study on the relationship between central D2 receptor occupancy and serum perphenazine concentration.

RATIONALE: There is a need for laboratory measures to guide clinical treatment with antipsychotic drugs. For serum concentration of the classical antipsychotic drug perphenzine an optimal therapeutic interval has been identified between 2 and 6 nmol/l. Positron emission tomography (PET) studies have suggested an optimal interval in central dopamine D2 receptor occupancy of between 65 and 80%. OBJECTIVES: The aim of the present cross-validation study in clinically stable schizophrenic patients was to examine the relationship between the optimal interval in central D2 receptor occupancy and the therapeutic window for serum perphenazine concentration. METHODS: Six patients who had responded to maintenance treatment with perphenazine decanoate were examined with PET and [11C]raclopride during steady-state conditions. Blood sampling was carried out for minimum serum perphenazine concentration and during the PET examination. RESULTS. The serum perphenazine concentration was between 1.8 and 9 nmol/l and the D2 receptor occupancy varied between 66 and 82%. The relationship between central receptor occupancy and serum drug concentration was curvilinear. Mild extrapyramidal symptoms were present in the patient with the highest D2 receptor occupancy. CONCLUSIONS. The previously suggested therapeutic window in serum perphenazine concentration is in good agreement with the optimal interval suggested for central D2 receptor occupancy. Serum concentrations at low dose levels may therefore serve as a useful tool in clinical monitoring of antipsychotic drug treatment.

Adult↗
PubMed1995

Quantitative determination of perphenazine and its metabolites in plasma by high-performance liquid chromatography and coulometric detection.

An accurate, reliable method has been developed for the therapeutic monitoring of perphenazine (PPZ) and its major metabolites in human plasma samples. Steady-state plasma levels of PPZ and its metabolites were quantitated for 30 elderly patients (mean age: 75) undergoing concurrent treatment with nortriptyline (NT) and PPZ, doses ranging from 4 to 32 mg/day for PPZ. The assay was suitable with patients on concurrent medications, and smaller patient plasma volumes (1 ml) were used indicating sufficient sensitivity and specificity. After plasma extraction and separation on a Nucleosil 5-microns C18 column, the recoveries (mean +/- S.D.) of PPZ and its metabolites were determined; perphenazine 92 +/- 7.5%, deshydroxyethylperphenazine 81 +/- 7.2%, perphenazine sulfoxide 68 +/- 6.4%, and 7-hydroxyperphenazine 45 +/- 5.5%. The assay also had limits of quantitative detectability for PPZ and its metabolites as follows: perphenazine 0.5 ng/ml, deshydroxyethylperphenazine 1.0 ng/ml, perphenazine sulfoxide 0.5 ng/ml, and 7-hydroxyperphenazine 5 ng/ml. Inter-assay reproducibility (C.V.) for the quality controls and patient samples ranged from 18.8 to 2.4%. The sensitivity and reproducibility of this method should improve PPZ therapeutic drug monitoring and research on interactions in depressed geriatric patients.

Aged↗
PubMed1998

The effects of perphenazine and bromocriptine on follicular dynamics and endocrine profiles in anestrous pony mares.

Nineteen anestrous pony mares were used in a project designed to determine the effects of altered prolactin concentrations on follicular dynamics and endocrine profiles during spring transition. The dopamine antagonist, perphenazine, was administered daily to mares (0.375 mg/kg body weight) in Group A (n = 6), while Group B mares (n = 7) received 0.08 mg/kg metabolic weight (kg75) dopamine agonist, 2-bromo-ergocriptine, intramuscularly twice daily. Mares in Group C (n = 6) received 0.08 mg/kg75, i.m., saline twice daily. Treatment began January 20, 1994, and continued until ovulation occurred. Mares were teased 3 times weakly with an intact stallion. The ovaries of the ponies were palpated and imaged weekly using an ultrasonic B-mode unit with a 5 Mhz intrarectal transducer until they either exhibited estrual behavior and had at least a 20-mm follicle, or had at least a 25-mm follicle with no signs of estrus. At this time, ovaries were palpated and imaged 4 times weekly. Blood samples were obtained immediately prior to ultrasonic imaging for measurement of prolactin, FSH and estradiol-17 beta. Perphenazine treatment advanced the spring transitional period and subsequent ovulation by approximately 30 d. Group A exhibited the onset of estrual behavior earlier (P < 0.01) than control mares. In addition, Group A mares developed large follicles (> 30 mm) earlier (P < 0.01) than Group B mares, with least square means for Groups A and B of 47.0 +/- 8.8 vs 88.1 +/- 8.2 d, respectively. Control mares developed 30-mm follicles intermediate to Groups A and B at 67.3 +/- 8.8 d. Bromocriptine decreased (P < 0.05) plasma prolactin levels throughout the study, while perphenazine had no significant overall effect. However, perphenazine treatment did increase (P < 0.05) mean plasma prolactin concentrations from Day 31 to 60 of treatment. There were no differences in mean plasma FSH or estradiol-17 beta between treatment groups. We concluded that daily perphenazine treatment hastened the growth of follicles and subsequent ovulation while bromocriptine treatment appeared to delay the growth of preovulatory size follicles without affecting the time of ovulation.

Anestrus↗
PubMed1976

Artificial induction of lactation by hypothalamic implantation of perphenazine in virgin goats.

Perphenazine (0-8-1 mg) caused udder growth and artificial induction of lactation, when stereotaxically implanted into the median eminence of virgin female goats. Sham implantations into the median eminence or implantation of perphenazine into sites of the hypothalamus not in the immediate proximity of the median eminence were ineffective. Fourteen-twenty-two d after implantation the goats were milked for the first time. Maximal milk yields of 250-1050 ml/d were achieved 3-5 months later. Udder development and induction of lactation during the premilking period were exclusively due to the action of perphenazine. It is likely that after implantation the milking stimulus played a synergic role with perphenazine in the progressive increase and the maintenance of lactation. Apparently no side effects were caused by the drug. Implantation of small doses of perphenazine in the hypothalamus might be a suitable technique for studying the physiological effects of increased levels of endogenous prolactin in goats.

Animals↗
PubMed1998

Prophylaxis for vomiting by children after tonsillectomy: ondansetron compared with perphenazine.

We have compared the effects of ondansetron and perphenazine on vomiting after tonsillectomy in 216 healthy children, aged 2-12 yr. The study was randomized, stratified, blocked and double blind. Anaesthesia was induced with propofol i.v. or by inhalation of halothane and nitrous oxide. Ondansetron 150 micrograms kg-1 or perphenazine 70 micrograms kg-1 was administered i.v. after induction of anaesthesia in a double-blind manner. Perioperative management of emesis, pain, fluids and patients discharge were standardized. Ondansetron and perphenazine had similar effects on postoperative vomiting (44% vs 41%; ondansetron vs perphenazine P = 0.77). By logistic regression analysis, the only significant predictor of postoperative vomiting was sex, that is males had a greater incidence of vomiting (49% vs 35%; P = 0.016). In-hospital vomiting was associated with a prolongation of stay in the day-care surgical unit of 7 min per episode of vomiting (P = 0.015). We conclude that ondansetron and perphenazine had similar effects on vomiting in children after tonsillectomy in a day-case setting.

Ambulatory Surgical Procedures↗
PubMed1989

Prediction of the optimal perphenazine decanoate dose based on blood samples drawn within the first three weeks.

During a 3-month period, 52 paranoid psychotic inpatients were treated with perphenazine decanoate (Trilafon decanoate) in order to determine a treatment schedule ensuring perphenazine serum levels within the optimal range (2-6 nmol/L). All patients received 1 ml (108 mg) perphenazine decanoate on days 0, 7 and 21, after which the doses and intervals were individually adjusted according to the clinical condition. It was shown that the sum of 2 measurements of perphenazine concentration early during treatment, viz., on days 14 and 21, correlates strongly (r = 0.96) with the steady-state level obtained after 3 months. Consequently, a nomogram for dose and length of interval could be elaborated giving steady-state serum levels of perphenazine of about 4 nmol/L, i.e., in the middle of the optimal concentration range.

Adolescent↗
PubMed1979

Effect of the timing of perphenazine administration on pregnancy in the rat.

Perphenazine in doses of 10--50 mg kg-1 day-1 given at the early stages of pregnancy delayed nidation up to day 8 of pregnancy. Once nidation had occurred the length of the rest of the gestation period was normal. Doses of up to 20 mg perphenazine kg-1 day-1, injected on days 1--7, prolonged gestation but the mothers and young were apparently normal; lower doses were effective only when treatment commenced soon after copulation. The delay in implantation of the ovum caused by perphenazine was corrected and and implantation was brought about immediately, by injection of 0.1 microgram oestradiol together with perphenazine. It is suggested that perphenazine delays and prevents implantation in rats by counteracting oestrogen release from the ovaries.

Animals↗
PubMed2002

Use of perphenazine to control cannibalism in DBA/1 mice.

Maternal administration of perphenazine decreased the incidence of cannibalism in colonies of interferon-gamma, interleukin (IL-4, IL-10, and IL-12) knockout mice of the DBA/1 and C57BL/6 background strains. This colony had high incidence of neonatal death due to cannibalism in approximately 50% of the pups. Perphenazine was administered to the dams in the drinking water, beginning on the day before or the morning of parturition. The medicated water was supplied at two dosages: 0.5 mg/ml and 0.025 mg/ml, resulting in a dosage of 4 mg/kg of body weight and 2 mg/kg, respectively, to the dams. Dams that were treated with perphenazine weaned 76.4% of their pups, compared with nontreated dams that weaned only 59.4% of their pups. Timing of the administration of perphenazine did not have a significant impact on efficacy; also, both doses were equally effective at preventing cannibalism. These findings indicate that perphenazine can modify poor maternal behavior such as cannibalism, resulting in more efficient production of valuable knockout mice.

Animals↗
PubMed2005

[Differentiation-inducing effects of perphenazine on K562 leukemia cells].

OBJECTIVE: To determine the differentiation-inducing effects of perphenazine on K562 leukemia cells. METHODS: Differentiation-Inducing effects of a phenothiazine perphenazine were evaluated by proliferation, morphology and function of K562 cells. We evaluated the effects of perphenazine on K562 cells proliferation by cellular enumeration in liquid culture assay, MTT assay and clony formation assay, the morphology by Wight-Gimesa staining, and the function by detecting CD71 through flow cytometry. RESULTS: Perphenazine enhanced the expression of CD71 on K562 cells and increased Hb content in K562 cells, while inhibited the proliferation of K562 cells. K562 cells showed differentiation morphology after the drug treatment. CONCLUSION: Perphenazine possessed differentiation-inducing effects on K562 cells.

Cell Transformation, Neoplastic↗
PubMed1991

[Therapy control of perphenazine. 2. Clinical aspects].

Rational use of serum concentration monitoring of the neuroleptic, perphenazine, was evaluated in a prospective investigation. A total of 141 hospitalized patients with paranoid symptoms (excluding mania) requiring treatment were included during the investigation period (one year). Perphenazine was administered (fixed doses) orally (92 patients) and parenterally (depot, decanoate, 45 patients) in a six-week treatment period. Serum concentrations of perphenazine were monitored after 10-14 days oral treatment, on the 14th and 21st days after the commencement of depot treatment. The patients were steered on to the recommended therapeutic range for perphenazine (1.5-6 nmol), according to the serum level measured. Global clinical assessment was carried out by the departmental physicians. Therapy control of perphenazine by serum monitoring was an important supplement to the clinical evaluation of therapeutic effect. Fifteen (65%) out of 23 patients who were treated orally with insufficient therapeutic effect, showed non-compliance or elevated metabolism. On the basis of a single serum concentration measurements (12 hours values), it proved possible to steer the majority of patients onto the recommended therapeutic level. In this way, the individual patient reached optimal therapeutic effect with a minimum of side-effects.

Adult↗
PubMed1985

Long-term depot neuroleptic treatment with perphenazine decanoate. I. Efficacy and side effects in a 12 month study of 42 drug monitored psychotic patients.

In an open, prospective 12 month study of perphenazine decanoate (PD), 42 psychotic patients diagnosed according to DSM-III were treated with a fixed depot interval and an individual dose, guided by gas chromatographic perphenazine plasma concentration monitoring combined with clinical evaluation. Degree of illness was rated using a social-psychiatric CGI-scale and extrapyramidal side effects were evaluated by means of a modified Simpson and Angus rating scale. After six months of treatment, a statistically significant improvement was found (p less than 0.001). During the last six months a further slight reduction in mean CGI-scores was observed. Mild to moderate extrapyramidal side effects occurred in 9 patients (21%) principally during the initial phase of therapy. No other side effects or changes in blood chemistry were found during the study. Plasma concentrations of perphenazine increased during the initial 3 months and stabilized hereafter. There were however, large intra- and inter-individual variations in the perphenazine plasma concentration/dose ratio. In addition, it was observed that plasma concentrations of perphenazine were significantly higher in patients who had been treated with neuroleptics for more than 10 years compared to those who had been treated 5 years or less. This observation indicates gradual development of tolerance to neuroleptic treatment. This study demonstrates that PD is a safe and effective remedy for maintenance therapy in psychotic patients.

Adult↗
PubMedDate not supplied

Antiemetic effect of perphenazine versus prochlorperazine intravenously before cisplatin therapy.

Antiemetic effects of perphenazine and prochlorperazine, both administered by continuous i.v. infusion after a loading dose, were compared in patients receiving cisplatin. Study subjects were 6 men and 13 women for whom other antiemetic therapy had failed; each patient was studied during two courses of cisplatin therapy. Patients were randomly selected to receive either perphenazine or prochlorperazine during the first course; for the second course, each received the other antiemetic. During drug administration, nausea, retching, vomiting, and side effects of the antiemetic were recorded hourly by the patient and concurrently by a pharmacist observer (both blinded). Each patient's scores on nausea, retching, and vomiting were compared by drug and by treatment sequence. Evaluable data for 17 patients showed that aggregate differences between responses to the two drugs were not significant. Fourteen patients had significantly less nausea, retching, and vomiting during the second course of treatment. Few side effects were reported. Nervousness was experienced with prochlorperazine in four patients and perphenazine in one, and drowsiness occurred with prochlorperazine in four patients and perphenazine in three. Perphenazine and prochlorperazine, when given in equal doses and administered by continuous i.v. infusion after a loading dose, were equally effective in controlling nausea and vomiting associated with cisplatin therapy.

Adult↗
PubMed1982

Amitriptyline-perphenazine and doxepin in depressed outpatients: a controlled double-blind study.

Amitriptyline-perphenazine (100/8-150/12 mg/day) and doxepin (100-150 mg/day) were compared for clinical efficacy and safety in a sample of 130 nonpsychotic depressed outpatients. Maximum study duration was 4 weeks; 19 amitriptyline-perphenazine and 29 doxepin patients completed less than or equal to 3 weeks of treatment and 45 amitriptyline-perphenazine and 37 doxepin patients completed 4 weeks of treatment. Patients in both groups showed significant improvement in depression, but amitriptyline-perphenazine produced greater improvement than doxepin on several measures of depressive symptomatology. The incidence of anticholinergic and sedative side effects was higher in the amitriptyline-perphenazine treated group.

Adult↗
PubMed1994

Acute and chronic toxicity of "Polfa" perphenazine.

The toxicity of "Polfa" perphenazine and its profile of pharmacological properties were estimated. LD50 values calculated in rats were 2000 mg/kg and 325 mg/kg, after p.o. and i.p. administration respectively. Chronic toxicity of the perphenazine was evaluated during the period of 3 month of the drug treatment p.o. or i.p. in the rats and mice. Decrease of the locomotor activity of perphenazine was observed after the highest dose (15 mg/kg) of the drug, only in the first weeks of the experiment. Also the cataleptogenic effect of perphenazine observed in the mice was diminished during 3 month of the experiment. Moreover, perphenazine did not induced significant changes in the blood morphology and histology of the internal organs.

Animals↗
PubMed1993

Efficacy of the combination of fluoxetine and perphenazine in the treatment of psychotic depression.

BACKGROUND: The aim of this study was to examine the efficacy of the combination of fluoxetine plus perphenazine in the treatment of psychotic depression. METHOD: Thirty patients who met DSM-III-R criteria for major depression with psychotic features were treated with fluoxetine plus perphenazine for 5 weeks. Patients were assessed at baseline and weekly using the Hamilton Rating Scale for Depression (HAM-D), Brief Psychiatric Rating Scale (BPRS), and a side-effect checklist that included specific extrapyramidal and anticholinergic side effects. RESULTS: Twenty-two (73%) of the 30 patients had a 50% or greater reduction in total HAM-D by Week 5. There was a significant improvement in HAM-D and BPRS scores at each week compared with baseline scores. Side effects reported by the patients included dry mouth (40%), blurry vision (40%), constipation (40%), tremor or rigidity (40%), and orthostatic hypotension or dizziness (27%). CONCLUSION: Fluoxetine when used in combination with perphenazine for the treatment of patients with psychotic depression has a response rate similar to the reported rates of response for tricyclic antidepressants (TCAs) plus antipsychotics, amoxapine, and electroconvulsive therapy. The side effects produced by the fluoxetine plus perphenazine combination were less than what has been reported for TCA plus antipsychotic treatment of psychotic depression and similar to the side effects reported with amoxapine. These data suggest that the combination of fluoxetine and perphenazine is effective for the treatment of psychotic depression and may be easier for patients to tolerate than a TCA plus antipsychotic.

Adult↗
PubMed1979

Treatment of secondary depression in schizophrenia. A double-blind, placebo-controlled trial of amitriptyline added to perphenazine.

The combination of antidepressants and neuroleptics has been widely recommended and commonly used clinically for the schizophrenic patient who becomes depressed. However, the value of the combination for these patients has not been clearly demonstrated. This report presents results of a double-blind, randomized, placebo-controlled clinical trial designed to evaluate the combination of perphenazine and amitriptyline hydrochloride with that of perphenazine alone in the treatment of 35 ambulatory chronic schizophrenic patients in whom depressive symptoms developed. Results showed that the addition of amitriptyline to perphenazine, when compared with perphenazine alone, was more effective in reducing symptoms of depression after four months of treatment, but less effective in reducing thought disorder. The study concludes that the value of adding an antidepressant to the usual neuroleptic in the treatment of secondary depression in schizophrenia should be reviewed.

Adolescent↗
PubMed1982

Serum prolactin level increase in normal subjects following administration of perphenazine oral dosage forms: possible application to bioavailability testing.

Two pilot studies were performed to determine if oral phenothiazine products could generate a significant increase in serum levels of the hormone prolactin. The two studies employed three and four healthy normal male subjects, respectively. In the first study the subjects received a screening dose, a placebo, one 8-mg perphenazine tablet, and two 8-mg perphenazine tablets. In the second study, the subjects were dosed with two 10-mg amitriptyline tablets, one 10-mg amitriptyline tablet with one combination tablet containing 10 mg of amitriptyline and 4 mg of perphenazine, and two combination tablets, each containing 10 mg of amitriptyline and 4 mg of perphenazine. In both cases the drug treatments produced a significant rise in the serum prolactin levels versus a placebo or control. This increase was defined as a prolactin response. The possible utility of this response in bioavailability testing is discussed.

Adolescent↗
PubMed1991

Perphenazine decanoate and cis(z)-flupentixol decanoate in maintenance treatment of schizophrenic outpatients. Serum levels at the minimum effective dose.

Two groups of schizophrenic outpatients were treated with perphenazine decanoate (N = 20) and cis(z)-flupentixol decanoate (N = 24) respectively. Every 3 months the dose was gradually reduced until symptoms appeared that were suggestive of a prodromal phase of a psychotic episode. A slightly higher dose was then promptly reinstituted (the minimum effective dose). At each dose level, two blood samples were drawn for determination of serum concentration. The mean minimum effective dose of perphenazine decanoate was 99.3 mg/2 weeks (range 21.6-270.5), while the mean minimum effective dose of cis(z)-flupentixol decanoate was 60 mg/2 weeks (range 20-250). The corresponding mean serum level of perphenazine decanoate was 7.3 nmol/l (range 2.0-18.1) and of cis(z)-flupentixol decanoate 7.8 nmol/l (range 1.2-37.0). There was a significant correlation between the administered doses and the corresponding serum levels for both drugs (r = 0.87, P less than 0.01). A weak positive correlation was found between serum levels at the minimum effective dose and symptom intensity (BPRS total score) (r = 0.53, P less than 0.02) for perphenazine, but not cis(z)-flupentixol. No correlation was found between serum levels and side effects or length of neuroleptic treatment. It is concluded that the serum drug concentrations corresponding to the lowest effective dose are so variable that routine serum level monitoring may be of limited value in the long-term maintenance treatment of schizophrenia.

Adult↗