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PubMed1982

Influence of nandrolone decanoate on the repopulation of the thymus after total body irradiation of mice.

It has been reported that nandrolone decanoate is helpful in overcoming the neutropenic phase following irradiation. In the present study the influence of nandrolone decanoate on the thymus' cellularity after total body irradiation was investigated. In comparison with a placebo-treated group, mice receiving nandrolone decanoate showed a similar pattern of thymus repopulation, but a significantly lower number of thymocytes over the whole period of treatment was found. Nonirradiated mice also had a significantly lower number of thymocytes when treated with nandrolone decanoate. In addition, the number of circulating leukocytes was also evaluated over a period of 1 month after total body irradiation. On 11 of the 21 days investigated, a significantly higher number of leukocytes was found in the nandrolone decanoate-treated group. We conclude that the action of nandrolone decanoate was not clearly distinct from that of testosterone regarding either granulopoiesis or thymic involution.

Animals↗
PubMedDate not supplied

Absorption of intramuscularly administered [14C]haloperidol decanoate in rats.

When [14C]haloperidol decanoate, an ester of haloperidol and decanoic acid, was given intramuscularly to rats, levels of total radioactivity and haloperidol decanoate in medial iliac and hypogastric sacral lymph nodes nearest to injection sites were the highest in examined lymph nodes and plasma. These lymph node levels became maximum 16 days after administration and declined gradually with half-life (around 14 days) similar to those of plasma total radioactivity, haloperidol decanoate and haloperidol. However, when the labelled ester was given intravenously, plasma total radioactivity disappeared far more rapidly. Much more radioactivity was found in hind limbs whose femoral muscles had been injected than in other body parts, even at late stages after administration. Haloperidol alone was found in the brain after [14C]haloperidol decanoate was given either intramuscularly or intravenously. It was concluded that haloperidol decanoate injected in rat femoral muscle was rate-limitedly distributed in lymph circulation and that the absorbed ester did not penetrate the brain through the blood-brain barrier but formed haloperidol did.

Absorption↗
PubMed1991

Pharmacokinetics of haloperidol decanoate in rats.

Plasma levels of haloperidol decanoate and haloperidol after intramuscular administration of haloperidol decanoate in rats showed good fits with a multi-compartment model which was constituted by combination of 2-compartment models for the disposition of haloperidol and for its ester decanoate through the process of hydrolysis of the ester. Calculated parameters indicated that most of intramuscularly administered haloperidol decanoate is absorbed in blood after hydrolysis to haloperidol and the absorption is rate-limiting. Regional lymph node levels suggested that the intramuscularly administered ester was absorbed via the lymphatic system where the hydrolysis to haloperidol probably occurred. Thus, slow entrance and hydrolysis of haloperidol decanoate in the lymphatic system was considered to be the cause of sustained plasma levels of the active principle after intramuscular administration of haloperidol decanoate.

Animals↗
PubMed2005

Long-term maintenance therapy with quetiapine versus haloperidol decanoate in patients with schizophrenia or schizoaffective disorder.

OBJECTIVE: To compare the long-term efficacy and tolerability of oral quetiapine with those of intramuscular haloperidol. METHOD: Patients with DSM-IV-diagnosed schizophrenia or schizoaffective disorder requiring long-term antipsychotic treatment were randomly assigned to open-label oral quetiapine or intramuscular haloperidol decanoate for 48 weeks. Clinicians were instructed to target dosing at 500 mg/day of quetiapine or 200 mg of haloperidol decanoate every 4 weeks. The Positive and Negative Syndrome Scale was used to assess efficacy; the Simpson-Angus Scale and the Barnes Akathisia Scale were used to assess safety and tolerability. For statistical analyses, a general linear mixed-model repeated-measures analysis of covariance was used, with change scores for dependent variables computed with the baseline score as covariate. Data were collected from 1998 to 2001. RESULTS: Thirty-five patients were enrolled, but 6 did not participate after being informed of their treatment assignment; 4 of the 6 withdrawals were assigned to haloperidol decanoate. Mean doses at week 48 were 493 mg/day of quetiapine (N = 16) and 170 mg/28 days of haloperidol decanoate (N = 9). Survival analysis showed no between-group differences in estimates of the number of patients remaining exacerbation-free over time. Both drugs were efficacious, but quetiapine was significantly better than haloperidol decanoate in controlling negative symptoms (p < .05). The incidence of extrapyramidal symptoms was low in both groups; patients receiving quetiapine showed significantly greater improvement in rigidity and akathisia (p < .05). CONCLUSION: Oral quetiapine was as efficacious as intramuscular haloperidol in preventing symptom exacerbation over 48 weeks in patients with schizophrenia or schizoaffective disorder, with fewer extrapyramidal symptoms, especially rigidity and akathisia. Quetiapine was more efficacious than haloperidol decanoate in treating negative symptoms.

Administration, Oral↗
PubMed1992

Positive and negative symptoms, depression and social disability in chronic schizophrenia: a comparative trial of bromperidol and fluphenazine decanoates.

A 1 year double-blind trial of bromperidol decanoate and fluphenazine decanoate was conducted in the maintenance treatment of 47 outpatients with schizophrenia. Six patients relapsed on bromperidol decanoate and none on fluphenazine decanoate, a difference which is statistically significant. No significant differences in positive and negative symptoms, nor depression measures were found between treatment groups when comparisons were made for change in score from entry to last visit. However, patients on fluphenazine decanoate achieved significantly better changes on social disability (Morningside scale) compared to those on bromperidol decanoate. The incidence of extrapyramidal side-effects was similar in both groups, and no statistically significant differences emerged in body weight change between treatments.

Adult↗
PubMed1986

[Effect of haloperidol decanoate on the dopaminergic system in the rat brain].

The effect of haloperidol decanoate and haloperidol on the dopaminergic system in the rat brain was studied. Each rat was treated with either once daily ip injection of haloperidol (5 mg/kg) for 4 weeks or a single sc injection of haloperidol decanoate followed by once daily ip injection of saline for 4 weeks. Three weeks after cessations of injections, the levels of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were determined in the striatum, limbic area and frontal cortex 4 hours after a single ip injection of haloperidol (1 mg/kg). The haloperidol decanoate-treated rats showed lower levels of DOPAC and/or HVA than the rats of the other two groups. The DA level was higher only in the limbic area of the rats treated with haloperidol decanoate than that of the rats treated with saline. There was no difference of the levels of DA and its metabolites between the saline and haloperidol-treated rats. These results indicate that the haloperidol decanoate-treated rats developed a tolerance to an acute effect of haloperidol on stimulation of DA turnover in the three areas examined, while the haloperidol-treated rats developed no tolerance under these experimental conditions. A single sc injection of haloperidol decanoate to rat is expected to produce a long lasting blocking of the central DAergic system for at least 7 weeks. Such a property of this drug appears favourable for the maintenance therapy of schizophrenia.

Animals↗
PubMed1986

Influence of nandrolone decanoate on weight loss in advanced non-small cell lung cancer.

The short term addition of nandrolone decanoate to combination chemotherapy given to patients with unresectable non-small cell lung cancer was evaluated in a randomized, prospective trial. Patients were treated with doxorubicin 50 mg/M2 intravenously, cyclophosphamide 300 mg/M2 intravenously, CCNU 50 mg/M2 orally, vincristine 1.4 mg/M2 intravenously, with and without cisplatin 50 mg/M2 intravenously, all given every 28 days. In addition, patients were randomized to receive either nandrolone decanoate 200 mg intramuscularly weekly for 4 weeks or no additional therapy. Patient age, disease extent, performance score, and pretreatment weight loss were similar in the two treatment arms. Objective antitumor response frequency was comparable on both treatment arms with median survival somewhat longer for patients receiving the androgen (median survival 5.5 months without and 8.2 months with nandrolone decanoate). There was a trend for less severe weight loss on the nandrolone decanoate arm (average weight loss 0.8 +/- 0.15 kg versus 0.21 +/- 0.18 kg, respectively), with half as many patients experiencing weight loss on nandrolone decanoate (25% versus 12%). A separate concurrent study has demonstrated decreased free testosterone levels in 66% of patients with advanced cancer studied prior to chemotherapy treatment, therefore, further prospective studies in which pretreatment testosterone levels are used to guide androgen administration are needed to define more precisely a role for androgen replacement therapy in non-small cell lung cancer.

Anabolic Agents↗
PubMed1989

Cross-over study of fat-corrected forearm mineral content during nandrolone decanoate therapy for osteoporosis.

We have previously reported an increase in forearm bone mineral content (BMC) during therapy for osteoporosis with the anabolic steroid, nandrolone decanoate. However, it has recently been claimed that part of this increase is spurious, due to a decrease in forearm fat during the treatment. We have therefore analyzed the data from a cross-over study of the effects of this agent on 70 osteoporotic women, using the fat correction procedure supplied by the manufacturer of the forearm densitometer. There was a significant rise (p less than 0.001) in the mean fat-corrected BMC (BMC[fc]) on nandrolone decanoate (50 mg intramuscularly every 2 or 3 weeks) and a non-significant fall in mean BMC[fc] off the drug. The mean time-weighted rate of change in the fat-corrected value was +29 +/- 5 mg/cm/year on nandrolone decanoate and -5 +/- 5 mg/cm/year off nandrolone decanoate (p less than 0.001). Nandrolone decanoate produces a significant gain in forearm mineral content even after allowing for changes in forearm fat content during therapy.

Aged↗
PubMed2006

Stereological study of the effects of nandrolone decanoate on the rat prostate.

It has been shown that nandrolone decanoate which is one of the anabolic-androgenic steroid compounds changes the testis structure and sperm quality but quantitative studies of the prostate have received less attention. Control rats received the peanut oil and experimental group received nandrolone decanoate for 14 weeks. Then the rats were left untreated for 14 weeks. After 14 weeks of withdrawal, the prostate was studied using stereological methods. The mean prostate weight decreased approximately 39% (p<0.009) in nandrolone decanoate treated rats. The mean total prostate volume, glands, epithelia, fluids and collagen bundles reduced approximately 30% (p<0.03), approximately 31% (p<0.03), approximately 41% (p<0.02), approximately 31% (p<0.05) and approximately 59.5% (p<0.02) in the experimental group. The mean total luminal surface of the glands and total length of the vessels decreased approximately 40% (p<0.02) and approximately 46% (p<0.009), respectively, in the nandrolone decanoate treated rats. The height of epithelium did show no difference. It can be concluded that nandrolone decanoate causes atrophic changes in the components of rat prostate.

Animals↗
PubMed1997

Effects of low temperatures (9-33 degrees C) and pH (3.3-5.7) in the loss of Saccharomyces cerevisiae viability by combining lethal concentrations of ethanol with octanoic and decanoic acids.

Octanoic and decanoic acids increase the rate of loss of Saccharomyces cerevisiae viability caused by lethal concentrations of ethanol, the specific death rate being an exponential function of the acid concentration. The highly liposoluble decanoic acid is the most effective. The fatty acids deleterious effect increases at pH below pKa (4.9) mainly due to the increase of the undissociated form concentration. The temperature effects (range 9 33 degrees C; at pH 3.9) on the kinetics of the toxin(s)-induced death suggest that the deleterious action of ethanol, octanoic acid and decanoic acid have the same biological target sites, probably related to transport processes across membranes, particularly the plasma membrane. In fact, the enthalpies of activation of octanoic acid- and decanoic acid-enhanced-ethanol-induced death were similar and close to the enthalpy of activation of ethanol-induced death. This average value (delta H++ = 11.4 +/- 2.7 kcal/mol) is of the order of magnitude of that of solute transport across plasma membranes. Results clearly suggest the important contribution of octanoic and decanoic acids, combined with ethanol, in the loss of yeast viability at the last steps of industrial ethanolic fermentations, particularly those carried out at low or intermediate temperatures. They also support the combination of lipophilic acids with low pH in food preservation.

Caprylates↗
PubMed2002

Characterization of bone mineral composition in the proximal tibia of cynomolgus monkeys: effect of ovariectomy and nandrolone decanoate treatment.

Life postmenopausal women, ovariectomized cynomolgus monkeys (Macaca fascicularis) experience accelerated loss of bone mass. Treatment of ovariectomized monkeys with nandrolone decanoate results in an increase in bone mass to levels comparable to those of intact animals. The changes in bone composition that occur with these treatments, however, are less well characterized. In the present study, we used synchrotron Fourier-transform infrared microspectroscopy (FT-IRM) and curve-fitting methods to monitor specific changes at cortical, subchondral, and trabecular bone regions in the proximal tibia. Four groups were studied: (1) sham-operated (sham); (2) ovariectomized and treated with placebo for 2 years (ovx); (3) ovx + nandrolone decanoate for 2 years (NAN); and (4) ovx + nandrolone decanoate beginning 1 year after ovx (dNAN). The results demonstrate that ovariectomy and nandrolone treatment did not affect the degree of mineralization as defined by the phosphate/protein ratio, but acid phosphate content (HPO(4)(2-)) in cortical and subchondral bone was increased by ovariectomy, suggesting this bone to be less mature due to increased remodeling that occurs after ovariectomy. In the subchondral and cortical bone regions, ovariectomized monkeys showed a lower total carbonate content (CO(3)(2-)/matrix ratio) than sham controls, specifically due to the decrease in labile carbonate content. In the trabecular region, no change of carbonate content was observed. Treatment with nandrolone decanoate was found to restore the loss in carbonate, where the resulting mineral had a larger quantity of type B carbonate. Finally, we correlated carbonate content with dual-energy X-ray absorptiometry measurements, and found a positive correlation between bone mineral density and type A carbonate in bone, which is stoichiometrically related to the amount of calcium in bone. Therefore, the results presented herein identify significant differences in bone chemistry after ovariectomy and nandrolone treatment, which may help explain previous findings that, although nandrolone decanoate treatment increased bone mass, it could not reverse the decrease in bone strength due to ovariectomy.

Anabolic Agents↗
PubMed2002

Nandrolone decanoate treatment induces changes in contractile responses of rat untrained fast-twitch skeletal muscle.

This investigation was designed to examine whether short-term administration of anabolic-androgenic steroids (AAS) (nandrolone decanoate) could produce changes in contractile responses of untrained rat fast- (edl) and slow- (soleus) twitch skeletal muscle. Twenty male rats were divided into two groups, one group received weekly (for 6 weeks) an intramuscular injection of AAS, nandrolone decanoate (15 mg kg(-1)) and the second group received weekly the similar doses of vehicle (sterile peanut oil). In edl intact isolated small bundles (two to four cells), it was found that nandrolone decanoate treatment increases the K+ contracture tension (146 mM) relative to maximum tension by 56%, whereas no change was observed in the time to peak tension and in the time constant of relaxation. By contrast, in treated soleus muscle, compared with control, no significant modification was found in the K+ contracture characteristics. The change in edl contractile responses was associated with a shift to more negative potential of the voltage-dependence activation and the steady-state inactivation curves which also shifted leftward in treated soleus fibres. Furthermore, in edl skinned Triton X-100 fibres, the Ca2+ sensitivity of contractile proteins (pCa50) was increased, while electrophoresis analysis indicates no significant effect of nandrolone decanoate treatment on myosin heavy chain (MHC) isoforms. The present results show that nandrolone decanoate treatment produces more pronounced changes in untrained fast muscle function rather than soleus by acting at different levels of the excitation-contraction coupling mechanism without changes in the MHC isoforms and that contractile responses became similar to those found in soleus muscle.

Animals↗
PubMed1995

Intestinal absorption and lymphatic transport of eicosapentaenoic (EPA), docosahexaenoic (DHA), and decanoic acids: dependence on intramolecular triacylglycerol structure.

We compared the absorption of eicosapentaenoic (EPA, 20:5n-3), docosahexaenoic (DHA, 22:6n-3), and decanoic acids in mesenteric lymph duct-cannulated rats following intragastric administration of two oils with different intramolecular triacylglycerol structures. One oil had a specific triacylglycerol structure with EPA and DHA located in the sn-2 position and decanoic acid in the sn-1 and sn-3 positions (specific M-n3-M) whereas the other oil had a random fatty acid distribution (random M-n3-M). The mol% (mol/100 mol total fatty acids) of fatty acids in the two oils was similar, with approximately 66 mol% of decanoic acid and 22 mol% of EPA and DHA. The lymphatic transport (microgram/min) of EPA and DHA as well as the mol% in the total lymph lipids were significantly (both P < 0.01) increased following intragastric administration of specific M-n3-M compared with random M-n3-M. The mol% of decanoic acid in the total lymph lipids was significantly (P < 0.01) higher after random M-n3-M compared with specific M-n3-M but the transport (microgram/min) of decanoic acid was not significantly different. We conclude that under our experimental conditions specific M-n3-M with EPA and DHA predominantly in the sn-2 position of the triacylglycerols was a more readily absorbed source of EPA and DHA and in this context should be investigated further for the potential use in clinical nutrition.

Animals↗
PubMed1987

A controlled trial of nandrolone decanoate in the treatment of rheumatoid arthritis in postmenopausal women.

To determine whether an anabolic steroid had any benefit in the treatment of rheumatoid arthritis 47 patients entered a parallel group study. Twenty four received nandrolone decanoate 50 mg intramuscularly every third week for two years and 23 patients received no anabolic steroids. Other therapy was unaltered. Patients attended for clinical and biochemical assessments as well as the objective assessments of elementary body composition by in vivo neutron activation analysis and measurement of the mineral content of the distal femur by single photon absorptiometry on five occasions. A modest clinical deterioration (except for grip strength) was seen in both groups. No significant changes in calcium or alkaline phosphatase were seen. There was no significant change in total body calcium, total body phosphorus, body weight, or bone index/bone width measurements in either group. Significant increases occurred in total body nitrogen, total body potassium, haemoglobin, and packed cell volume (by six months) in the group treated with nandrolone decanoate. Comparison of 10 patients in the group treated with nandrolone decanoate also receiving oral steroid therapy with 14 patients in this group not receiving oral steroid therapy showed no significant differences. The main side effect of nandrolone decanoate was hoarseness. No radiological changes were seen. Nandrolone decanoate, in a dose that produces a significant anabolic effect, has no demonstrable action on bone metabolism in rheumatoid arthritis but may improve the chronic anaemia by six months.

Anabolic Agents↗
PubMed1980

The effects of nandrolone decanoate on rarefying bone tissue.

The effects of nandrolone decanoate on rarefying bone tissue were studied with the aid of microradiography and fluorescence microscopy in tetracycline-labelled preparations of the rabbit calcaneus and the long bones of old dogs. Osteoporosis was induced in the rabbit calcaneus by resecting of the Achilles tendon. In 20 of the 24 rabbits treated with nandrolone decanoate, the osteoporosis observed was less severe than in 8 untreated controls. Furthermore, in comparison with the controls, the signs of active osteogenesis in the treated groups increased systematically. In the old dogs, nandrolone decanoate caused a new opposition, identified by tetracycline labelling, to appear at the periphery of the medullary cavity. All the observations suggest that nandrolone decanoate has a favourable effect on osteogenetic phenomena and probably an inhibitory action on bone resorption. Consequently, nandrolone decanoate is capable of preventing or, at least, of partially correcting losses of bone mass.

Animals↗
PubMed2004

Effects of nandrolone decanoate on VO2max, running economy, and endurance in rats.

PURPOSE: The aim of the present study was to determine the effects of treatment with an anabolic androgenic steroid (AAS), nandrolone decanoate, on the submaximal running endurance (SRE), maximum oxygen consumption (VO2max), running economy (VO2submax), and blood oxygen carrying capacity of endurance trained rats. METHODS: Forty male Wistar rats were randomly allocated into two groups: a sedentary group and an exercising group training on treadmill for 8 wk. Half of the trained and half of the sedentary rats received weekly either nandrolone decanoate (10 mg x kg(-1)) or placebo (Pl) for the last 6 wk of experiment. SRE and VO2max tests were performed several times for all four groups (N = 10 each).Red blood cells parameters were measured at the end of the experiment. RESULTS: The trained rats had increased their SRE compared with sedentary rats throughout the experiment. At the end of the trial, the trained rats receiving nandrolone decanoate ran 46% longer than trained rats receiving Pl during the SRE test (P < 0.05). At the end of the experiment, trained rats had greater maximal time to exhaustion and higher VO2max than those of the sedentary rats but there were no differences in VO2max, VO2submax, and red blood cells parameters between the trained rats receiving nandrolone decanoate and those receiving Pl. CONCLUSIONS: Nandrolone decanoate has no effect on the SRE, VO2max and VO2submax of untrained rats. AAS treatment combined with submaximal training enhances SRE more than training alone but exerts no additive effects on VO2max, running economy, and oxygen carrying capacity of blood. The results suggest that this improvement in SRE of trained rats is due to the impact of AAS on other factors involved in exercise adaptation.

Animals↗
PubMed1998

Nandrolone decanoate causes pathologic changes in the uterus of surgically postmenopausal female cynomolgus macaques.

OBJECTIVE: To determine the effects of the androgenic anabolic steroid nandrolone decanoate on uterine endometrium and myometrium and on the mammary gland of female cynomolgus macaques by using morphologic, histomorphometric, and histopathologic determinations. DESIGN: Histologic and histomorphometric measurements were performed on uteri and mammary glands that were collected at necropsy from animals that had been used in a long-term experiment to examine the effects of nandrolone decanoate on bone and coronary arteries. The animals were surgically postmenopausal cynomolgus macaques randomized into four treatment groups: (a) intact sham ovariectomized (sham; n = 12), (b) ovariectomized (OVX; n = 15), (c) ovariectomized + nandrolone decanoate for 2 years (OVX + ND; n = 14), and (d) ovariectomized + nandrolone decanoate for 1 year, beginning 1 year after ovariectomy (OVX + NDdelay; n = 11). Intramuscular injections of nandrolone decanoate (25 mg every 3 weeks) were given to the two nandrolone-treated groups of animals (OVX + ND and OVX + NDdelay): one starting 3 weeks after ovariectomy and continuing for 2 years and the other group 1 year after ovariectomy. The sham and OVX groups were given an intramuscular injection of sterile vehicle every 3 weeks. RESULTS: Nandrolone treatment was moderately uterotropic in all treated versus ovariectomized animals. Changes induced were an increase in uterine weight, endometrial thickness, and glandular area, and a high incidence of mucometra. Glandular architecture was altered by nandrolone treatment such that glands extended into the myometrium (producing an adenomyosis-like lesion). Mammary gland changes were mild and equivocal. CONCLUSION: Nandrolone induced pathologic changes in ovariectomized monkeys similar to adenomyosis in the uterus.

Anabolic Agents↗
PubMed1995

Monitoring plasma levels of fluphenazine during chronic therapy with fluphenazine decanoate.

This study was conducted to examine the interpatient variability in steady-state plasma concentrations of fluphenazine by repeat depot intramuscular administration, and to determine the relationship between these concentrations and clinical state. Steady-state pre-dose concentrations of fluphenazine in plasma were measured using a sensitive and specific gas chromatography/mass spectrometry (GC/MS) assay in 24 patients with schizophrenia who were receiving continuous treatment with depot intramuscular fluphenazine decanoate. Clinical response was measured using the Andreasen Scale for positive and negative symptoms. Steady-state plasma concentrations of fluphenazine ranged from undetectable (< 0.1 ng/ml) to 27.9 ng/ml, with a median of 0.5 ng/ml. No significant associations were found between plasma concentration and dosage, or age and sex of the patient. Steady-state plasma concentrations in patients taking anticholinergic agents were significantly higher than in patients not receiving such drugs (P < 0.05 by Mann-Whitney U-test). Poorer control, expressed as the sum of the negative symptom scores or the sum of the positive and negative symptom scores, was related to higher log transformed plasma concentration of fluphenazine and higher fluphenazine decanoate dosage. The log transformed plasma concentrations of fluphenazine and the fluphenazine decanoate dosages were weakly related. Patients receiving another antipsychotic drug in addition to fluphenazine decanoate tended to have poorer clinical control and higher dosages of fluphenazine decanoate. These results indicate the useful role that plasma level monitoring can fulfil in identifying patients who are therapy-resistant despite high plasma levels.

Adult↗