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Role of octanoic and decanoic acids in the control of seizures.

Octanoic and decanoic acid, the major constituents of the Medium Chain Triglyceride (MCT) Emulsion diet, have been detected in appreciable quantities in the peripheral blood of children with intractable seizures treated with the MCT diet. Serum concentrations of these acids as well as beta hydroxybutyrate and acetoacetate rose as the diet was introduced and on full diet showed pronounced diurnal variation and low concentrations in the morning. No correlation between octanoic and decanoic acid concentrations and control of seizures was established, but further studies with octanoic and decanoic acid using animal models are necessary to assess the role of these acids and of control of seizures.

3-Hydroxybutyric Acid↗

Antiparkinsonian agents and fluphenazine decanoate.

The author examined the incidence and severity of extrapyramidal symptoms (EPS) in 19 male psychotic outpatients receiving fluphenazine decanoate. Ten patients developed an EPS; only 3 had symptoms of the highest severity. The data suggest that neither prophylactic nor long-term use of antiparkinsonian agents is necessary for most patients receiving fluphenazine decanoate. On the basis of a comparison to a study of fluphenazine enanthate patients, the author concludes that fluphenazine decanoate is the drug of choice in terms of incidence and severity of EPS.

Adult↗

Pharmacokinetic parameters of nandrolone (19-nortestosterone) after intramuscular administration of nandrolone decanoate (Deca-Durabolin) to healthy volunteers.

Nandrolone decanoate (Deca-Durabolin) was injected intramuscularly into healthy volunteers. One group of females received one injection of 100 mg and three groups of males received one injection of 200 mg, two repeat injections of 100 mg or four repeat injections of 50 mg respectively. The serum levels of nandrolone (19-nortestosterone) were determined by radioimmunoassay and used to estimate pharmacokinetic parameters. The following pharmacokinetic parameters were found: a mean half-life of 6 days for the release of the ester from the muscular injection depot into the general circulation; a mean half-life of 4.3 h for the combined processes of hydrolysis of nandrolone decanoate and of distribution and elimination of nandrolone; a mean nandrolone serum clearance of 1.55 1 X h-1 X kg-1. The half-life of hydrolysis of nandrolone decanoate in serum was of the order of one hour or less. The data are consistent with linear kinetics.

Adult↗

Effects of resistance exercise training and nandrolone decanoate on body composition and muscle function among patients who receive hemodialysis: A randomized, controlled trial.

Patients who are on hemodialysis commonly experience muscle wasting and weakness, which have a negative effect on physical functioning and quality of life. The objective of this study was to determine whether anabolic steroid administration and resistance exercise training induce anabolic effects among patients who receive maintenance hemodialysis. A randomized 2 x 2 factorial trial of anabolic steroid administration and resistance exercise training was conducted in 79 patients who were receiving maintenance hemodialysis at University of California, San Francisco-affiliated dialysis units. Interventions included double-blinded weekly nandrolone decanoate (100 mg for women; 200 mg for men) or placebo injections and lower extremity resistance exercise training for 12 wk during hemodialysis sessions three times per week using ankle weights. Primary outcomes included change in lean body mass (LBM) measured by dual-energy x-ray absorptiometry, quadriceps muscle cross-sectional area measured by magnetic resonance imaging, and knee extensor muscle strength. Secondary outcomes included changes in physical performance, self-reported physical functioning, and physical activity. Sixty-eight patients completed the study. Patients who received nandrolone decanoate increased their LBM by 3.1 +/- 2.2 kg (P < 0.0001). Exercise did not result in a significant increase in LBM. Quadriceps muscle cross-sectional area increased in patients who were assigned to exercise (P = 0.01) and to nandrolone (P < 0.0001) in an additive manner. Patients who exercised increased their strength in a training-specific fashion, and exercise was associated with an improvement in self-reported physical functioning (P = 0.04 compared with nonexercising groups). Nandrolone decanoate and resistance exercise produced anabolic effects among patients who were on hemodialysis. Further studies are needed to determine whether these interventions improve survival.

Absorptiometry, Photon↗

Effects of nandrolone decanoate (Decadurabolin) on serum Lp(a), lipids and lipoproteins in women with postmenopausal osteoporosis.

Although lipoprotein(a) (Lp(a)) concentrations are mainly regulated genetically, it has been reported that variations in sex hormone concentrations may have effects on serum Lp(a). We evaluated the effect of nandrolone decanoate, a testosterone-derived synthetic anabolic steroid, on serum Lp(a), lipids and lipoproteins in 19 postmenopausal women who were given parenteral nandrolone decanoate (Decadurabolin) once a week for 3 weeks. At the 4th week, a significant decrease was observed for total cholesterol (p = 0.003), Lp(a) (p = 0.0003), apolipoprotein A-I (apo A-I) (p < 0.0001), and high density lipoprotein-cholesterol (HDL-C) (p < 0.0001). Moreover, a significant decrease in serum albumin concentration (p = 0.002) was concomitantly observed. We conclude that the administration of nandrolone decanoate significantly affects the lipid profile of postmenopausal women, showing controversial effects in terms of cardiovascular risk.

Anabolic Agents↗

A controlled trial of recombinant human erythropoietin and nandrolone decanoate in the treatment of anemia in patients on chronic hemodialysis.

We conducted a prospective, randomized study in chronic hemodialysis patients in order to determine whether the erythropoietic response to low dose recombinant human erythropoietin (rHuEpo) could be enhanced by administration with androgens. Patients received rHuEpo 40 U/kg intravenously three times weekly either alone (Group 1, n = 6) or with weekly intramuscular injection of 2 mg/kg nandrolone decanoate (Group 2, n = 6) for up to 16 weeks. Baseline hct, ferritin, N-terminal parathyroid hormone, and aluminum levels were similar. The mean weekly rate of rise in hct was 0.32 +/- 0.13% in Group 1 and 0.37 +/- 0.11% in Group 2, p = NS. Three of 6 patients in Group 1, but only 1 of 6 patients in Group 2, reached the target hct of 30% within 16 weeks. Two patients in Group 2 requested that the nandrolone decanoate be stopped prior to reaching target hct because of unacceptable side effects (acne). We conclude that many chronic hemodialysis patients appear to respond adequately to rHuEpo at the dose used in our study. Nandrolone decanoate does not enhance the response rate to this rHuEpo dose and is associated with significant side effects.

Anabolic Agents↗

[Effects of nandrolone decanoate on bone mineral content and intestinal absorption of calcium].

To evaluate the effects of a long-term treatment with nandrolone decanoate on metabolism of the skeleton, a double-blind randomized study was carried out in women with joint diseases without metabolic bone derangement. Ten patients were treated with 50 mg of nandrolone decanoate every three weeks for two years; in six subjects a treatment with placebo was performed. As it concerns plasma calcium and phosphate, serum alkaline phosphatase, urinary excretion of calcium, phosphate, hydroxyproline and cAMP, as parathyroid index, it was not observed significant differences in the two examined groups. While in placebo group at the end of the study the intestinal radiocalcium remained unchanged and bone mineral content showed a slight decrease, on the contrary nandrolone decanoate treatment promoted a significant improvement in intestinal calcium absorption and an increase in bone mineral content.

Adenosine Monophosphate↗

Restorative effects of nandrolone decanoate on the mononuclear phagocyte system in tumor-bearing mice.

The effects of nandrolone decanoate on the mononuclear phagocyte system (MPS) were examined in normal or tumor-bearing mice. Bactericidal activity against Listeria monocytogenes, carbon clearance test and leukocyte accumulation into the site of inflammation were depressed when viable cells of sarcoma-180 were inoculated subcutaneously into ddY mice 24hr before the assays. Pretreatment with nandrolone decanoate prevented such depression in tumor-bearing mice and increased MPS activities of normal or tumor-bearing mice above the level of non-treated normal mice. Nandrolone decanoate may be useful for the augmentation of antimicrobial activity in tumor-bearing hosts.

Anabolic Agents↗

Fluphenazine decanoate, fluphenazine hydrochloride given orally, and placebo in remitted schizophrenics. I. Relapse rates after one year.

In a simple remitted, nonpsychotic schizophrenics, the relapse rate within one year was significantly higher for those patients taking placebo as opposed to those taking fluphenazine hydrochloride orally or fluphenazine decanoate. There were no differences in relapse rates between the two active drugs, but there were significantly more terminations due to toxicity from fluphenazine decanoate than from pluphenazine given orally, entirely due to the fact that in 35% of patients receiving fluphenazine decanoate, severe akinesia developed.

Acute Disease↗

D2-dopamine-receptor occupancy during treatment with haloperidol decanoate.

We investigated in an open, explanatory study a total of 24 patients meeting DSM-III-R criteria for schizophrenia. Eighteen patients were treated for at least 4 weeks with a fixed dose of orally administered haloperidol for at least 4 weeks (mean daily dosage ranging from 0.07 to 0.35 mg/kg b.w.), and 6 patients received haloperidol decanoate with a fixed dose for at least 4 months (dosage range 50-150 mg/4 weeks; calculated mean daily dosage ranging from 0.02 to 0.09 mg/kg b.w.). One week after injection of haloperidol decanoate, the single photon emission computed tomography examination was performed. Our data suggest that D2-dopamine-receptor occupancy of 50 mg/4 weeks haloperidol decanoate 1 week after injection corresponds to an oral dose of 4.5 mg/day haloperidol.

Adult↗

Efficacy and tolerability of flupenthixol decanoate in the treatment of depression and psychosomatic disorders: a multicenter trial in general practice.

1. A number of controlled as well as uncontrolled studies indicate that flupenthixol in a low-dose regimen is effective in treating syndromes with depression, anxiety, and psychosomatic disorders. 2. In view of the low compliance rates among patients suffering from depressive syndromes, the author evaluated the efficacy and tolerability of flupenthixol decanoate i.m. in an unselected collective of such patients treated in general practices. 3. Flupenthixol decanoate i.m. induced remission in 25% of patients suffering from chronic pain, in 29% of patients with psychosomatic disorders. Patients with depression and anxiety remitted in 27% of the cases. Therapeutic benefit was seen in more than 90% of the patients. 4. The best results were observed in patients 1) who had not been treated with psychotropic drugs before, 2) whose disease had a duration of less than one year, 3) who were under 40 years of age, and 4) who were treated with a dose lower than 0.5 ml (10 mg flupenthixol decanoate).

Adolescent↗

Haloperidol plasma 'threshold' levels for relapse prevention in schizophrenia: a study with haloperidol decanoate.

Forty-eight schizophrenic outpatients treated with flexible doses of haloperidol decanoate were followed up in a naturalistic fashion for 3 years with periodic monitoring of clinical symptoms, side effects and haloperidol plasma concentrations. There was no relationship between plasma level and clinical response, however categorical data analysis showed that patients with plasma levels over 4 ng/ml had a significantly reduced relapse rate compared with patients with plasma levels below this plasma 'threshold' level. This effect could be observed during the first, second as well as third year of treatment. The relapse rate did not change significantly in relation to time (during years 1, 2, 3), when patients with haloperidol plasma levels below and equal to or over 4 ng/ml were considered separately. In patients with haloperidol equal to or over 4 ng/ml, the variability (measured as coefficient of variation %) in the total scores of SAPS and SANS was lower, indicating a better clinical stability. These data are in fairly good agreement with other literature findings showing that an indiscriminate dose reduction strategy during long-term treatment of schizophrenic disorders with haloperidol decanoate should be discouraged, since it leads to an increase in the relapse rate. Before deciding about a dose reduction, clinicians should take into careful consideration some clinically relevant variables (i.e. frequency of previous relapses, severity of symptoms, iatrogenic depression, risk for development of extrapyramidal side effects) for each patient. A better clinical stability during treatment with haloperidol decanoate can be obtained when plasma 'threshold' levels for response are reached.

Adult↗

Fluphenazine plasma level monitoring for patients receiving fluphenazine decanoate.

BACKGROUND: Finding a dose of an antipsychotic for maintenance therapy that is both safe and effective can be difficult because clinicians are unable to titrate dose against clinical response in patients who are already stable. Therapeutic monitoring of antipsychotic plasma levels has the potential for helping clinicians in dosage selection. With this in mind, we evaluated the usefulness of monitoring fluphenazine plasma levels for patients with schizophrenia who were receiving maintenance treatment with fluphenazine decanoate. METHOD: Thirty-one patients with schizophrenia were randomly assigned to low, medium, or high (0.1-0.3, 0.3-0.6, 0.6-1.0 ng/ml) plasma levels of fluphenazine. The dose of fluphenazine decanoate was adjusted in order to maintain patients in their assigned range. Side effects, psychopathology, and psychotic exacerbations were measured during the year following randomization. RESULTS: All of the psychotic exacerbations occurred during the first eight weeks following randomization, before patients had adequate time to reach their plasma level assignments. We did not find a relationship between plasma levels of fluphenazine and clinical outcomes or side effects. CONCLUSION: Our results do not provide support for the usefulness of monitoring fluphenazine plasma levels for patients receiving fluphenazine decanoate.

Adult↗

The roles of depot injection sites and proximal lymph nodes in the presystemic absorption of fluphenazine decanoate and fluphenazine: ex vivo experiments in rats.

PURPOSE: The release and presystemic absorption of fluphenazine and its decanoate ester from intramuscular depots were investigated. METHODS: Rats were sacrificed in groups of three at various times after injection of drug or prodrug in sesame oil. Muscle tissues at the injection sites and various lymph nodes were excised. Blood (plasma) was harvested by cardiac puncture. RESULTS: Following administration of fluphenazine decanoate, the amount of prodrug at the sites of injection declined exponentially (half-life 3.4 days). Highest concentrations of drug and prodrug were found in iliac and hypogastric lymph nodes nearest to injection sites in which both analytes were detectable 28 days post dose. The half-life for the decline of fluphenazine from lymph nodes (4.6 days) was similar to that from plasma (4.3 days). Following administration of fluphenazine base, only 2.8% of the dose remained at the sites of injection after 2 days. Concentrations of drug in iliac and hypogastric lymph nodes were comparable to those in distal lymph nodes. Fluphenazine concentrations in the lymphatic tissues decreased at about the same rate as plasma concentrations. CONCLUSIONS: The rate limiting step appeared to be slow partitioning of the decanoate from oily deposits at the injection site and proximal lymph nodes with subsequent hydrolysis of the ester group.

Absorption↗

19F-magnetic resonance spectroscopy and chemical shift imaging for schizophrenic patients using haloperidol decanoate.

Haloperidol decanoate is widely used in the maintenance treatment of schizophrenia and other psychotic disorders, but knowledge concerning its pharmacokinetics at the injected region is very limited. Because the chemical structure of haloperidol contains fluorine, in vivo 19F-magnetic resonance (MR) spectroscopy (repetition time (TR) = 1 s) and chemical shift imaging (CSI; TR = 1 s, pixel size = 15 x 15 mm) were performed in schizophrenic patients who were treated with haloperidol decanoate (three men and one woman) to measure its diachronic change at the injection point and visualize its local distribution after intramuscular injection. 19F signals (T1 time = 365 ms) were obtained at the haloperidol decanoate-injected region. The decrease rate of the signal-to-noise ratio (SNR) by 19F-MR spectroscopy seemed large in comparison with that of the plasma haloperidol concentration. The distribution was clearly visualized by 19F-CSI for a few days after the injection, but after 1 week could no longer be seen. Although the slow-release characteristics of depot neuroleptics have been explained by the slow diffusion of esterified neuroleptics from the oil vehicle, this result may suggest that there are other mechanisms involved in maintaining the plasma haloperidol concentration. In vivo 19F-MR spectroscopy and CSI are potentially applicable for the pharmacokinetic analysis of haloperidol and other drugs containing fluorine in their structure.

Adult↗

Body composition and anthropometry in bodybuilders: regional changes due to nandrolone decanoate administration.

The purpose of the present study was to investigate regional changes in body composition and anthropometric variables induced by nandrolone decanoate in bodybuilders. In a randomized, double blind, placebo controlled design 16 subjects received weekly intramuscular injections containing 200 mg nandrolone decanoate (ND) or placebo. Composition of total body and body parts were assessed using dual energy X-ray absorptiometry (DEXA), skinfolds and circumferences. Measurements were performed at baseline, after 8 weeks ND administration period and 6 weeks after drug withdrawal. DEXA revealed that total body mass (from 76.16 +/- 2.70 to 78.73 +/- 4.07 kg, p<0.5) and bone-free lean mass (from 59.54 +/- 2.36 to 63.06 +/- 2.99 kg, p < 0.025) increased significantly during ND administration whereas bone mineral mass remained unchanged. Six weeks after drug cessation bone-free lean mass was still increased compared to baseline levels. During ND administration significant increments of bone-free lean mass of the trunk (+ 2.03 kg) and legs (+ 1.08 kg) could be observed. Percentage fat of the legs decreased during the drug intervention period (-1.9%) and remained lowered six weeks after drug withdrawal. No alteration in any variable of the arms was observed. Skinfolds did not change during the entire study period in both groups. After 8 weeks ND administration circumference of the neck was increased (+0.9 cm) significantly although all circumferences underwent non-significant gains. In conclusion, the intramuscular administration of nandrolone decanoate (200 mg per week) during eight weeks induced an increase of body weight and bone-free lean body mass in bodybuilders that was mainly situated in the trunk and legs as determined by DEXA. The changes in the trunk were reflected in the circumferences but not the alterations in the legs. Skinfolds were not able to detect changes of fat mass of body parts. DEXA revealed that total fat mass and total percentage fat remained unaffected by drug administration while percentage fat of the legs decreased and remained lowered after drug cessation. These data indicate that changes of the composition of body parts induced by ND are elucidated less accurately by circumferences or skinfolds rather than by DEXA.

Absorptiometry, Photon↗

[Drug-response differences of high and standard dosage of fluphenazine-decanoate in relation to schizophrenic symptoms (author's transl)].

The treatment of schizophrenic patients with high-dosed neuroleptics is discussed. The drug-response difference between a low dose and a high dose of Fluphenazine-Decanoate was investigated in 40 chronic schizophrenic patients. All patients were resistant to standard doses of neuroleptics and were therefore treated with higher doses. All patients entering the study were treated for at least three months with high doses of Fluphenazine-Decanoate, i.e. 100 mg or more within three weeks. From this pool of 40 patients two groups were created at random for the doubleblind study: In one group the high dose was continued (average dose 225 mg/in 14 days), in the other group Fluphenazine-Decanoate was reduced to a standard-dose of 25 mg in 14 days. During the 24 weeks of investigation the somatic and psychopathological state of the patient was evaluated by means of the AMP-System. Furthermore the self-rating scale EWL-K was used. After 24 weeks the patients of the high-dosed group were more often rated as unchanged, while the patients in the standard-dosed group were evaluated significantly more often as better or worse. Average condition-differences between the both groups could not be found in a covariance-analysis. A factorial covariance-analysis showed that differences in the initial hostility-syndrome and catatonic-syndrome scores are predictors for a syndrom-relevant differential dosage per group. Patients with low hostility- and low catatonic-syndrome-scores improved after reduction of the doses in the apathic, the halluzinatoric-desintegrative and the neurological syndrome, whereas patients with high initial hostility- and catatonic-syndrome-scores became psychopathologically worse after dosage reduction. Finally the possibilities of generalizing from the results obtained to the relevance of high and standard neuropletic therapy are discussed.

Adult↗

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↗