A 12-week subchronic intramuscular toxicity study of risperidone-loaded microspheres in rats

2014 ◽  
Vol 34 (2) ◽  
pp. 205-223 ◽  
Author(s):  
J Zhang ◽  
L Ye ◽  
W Wang ◽  
G Du ◽  
X Yu ◽  
...  
Keyword(s):  
Sustained Release ◽  
Recovery Phase ◽  
Toxicity Study ◽  
Subchronic Toxicity ◽  
Release Formulation ◽  
Sustained Release Formulation ◽  
Long Acting ◽  
Pituitary Prolactin ◽  
Related Mortality

Long-acting injectable formulations of antipsychotics have been an important treatment option to increase the compliance of the patient with schizophrenia by monitoring drug administration and identifying medication noncompliance and to improve the long-term management of schizophrenia. Risperidone, a serotoninergic 5-HT2and dopaminergic D2receptor antagonist, was developed to be a long-acting sustained-release formulation for the treatment of schizophrenia. In this study, 12-week subchronic toxicity study of risperidone-loaded microspheres (RMs) in rats by intramuscular injection with an 8-week recovery phase was carried out to investigate the potential subchronic toxicity of a novel long-acting sustained-release formulation. The results indicated that the dosage of 10–90 mg/kg of RM for 2 weeks did not cause treatment-related mortality. The main drug-related findings were contributed to the dopamine D2receptor and α1-adrenoceptor antagonism of risperidone such as elevation of serum and pituitary prolactin levels and ptosis and changes in reproductive system (uterus, ovary, vagina, mammary gland, testis, seminal vesicle, epididymis, and prostate). In addition, foreign body granuloma in muscle at injection sites caused by poly-lactide-co-glycolide was observed. At the end of the recovery phase, these changes mostly returned to normal. The results indicated that RM had a good safety profile in rats.

Development of an injectable sustained-release formulation of morphine: antinociceptive properties in rats

1998 ◽  
Vol 32 (3) ◽  
pp. 270-275 ◽  
Author(s):  
R. A. R. Tasker ◽  
B. J. Connell ◽  
S. J. Ross ◽  
C. M. Elson
Keyword(s):  
Sustained Release ◽  
Subcutaneous Administration ◽  
Opioid Analgesics ◽  
Morphine Sulphate ◽  
Release Formulation ◽  
Sustained Release Formulation ◽  
Sterile Saline ◽  
Long Term Storage ◽  
Chitosan Gel

The antinociceptive actions of morphine incorporated into an injectable chitosan-based gel were investigated in rats. Subcutaneous administration of 4.8 mg/kg morphine sulphate in a gel composed of N,O-carboxymethylchitosan (NOCC) and chitosan resulted in significant antinociception within 10 min that was maximal at 60 min and persisted for 6 h. In contrast, the same dose of morphine sulphate injected in sterile saline produced maximal responses at 30 min but only persisted for 2 h. NOCC/chitosan gel was easily injectable using a 22 guage needle and appears stable in long-term storage. No local or systemic adverse effects other than morphine-induced sedation were observed either at the time of injection or during the subsequent 48 h. We conclude that gels composed of chitosan and chitosan derivatives are effective matrices for sustained-release formulations of opioid analgesics capable of providing long-lasting antinociception.

Pharmacokinetics and efficacy of the long-acting somatostatin analogue somatuline in acromegaly

1994 ◽  
Vol 130 (3) ◽  
pp. 229-234 ◽  
Author(s):  
MR Johnson ◽  
HS Chowdrey ◽  
F Thomas ◽  
C Grint ◽  
SL Lightman
Keyword(s):  
Sustained Release ◽  
Oral Glucose ◽  
Somatostatin Analogue ◽  
Oral Glucose Load ◽  
Glucose Load ◽  
Release Formulation ◽  
Sustained Release Formulation ◽  
Thyrotrophin Releasing Hormone ◽  
Igf I ◽  
Long Acting

Johnson MR, Chowdrey HS, Thomas F, Grint C, Lightman SL. Pharmacokinetics and efficacy of the long-acting somatostatin analogue somatuline in acromegaly. Eur J Endocrinol 1994;130:229–34. ISSN 0804–4643 The aim of this work was to assess the use of a sustained-release formulation of somatuline, a long-acting analogue of somatostatin, in the treatment of acromegaly. Fifteen patients with active acromegaly, as defined by random growth hormone (GH) levels greater than 10 mU/l, which fail to be suppressed to less than 5 mU/l following an oral glucose load, were studied. Somatuline was administered as an intramuscular injection in two regimens: eight patients were given a single injection of the sustained-release formulation and blood samples taken over the next month for the measurement of both basal levels of GH and the GH response to thyrotrophin-releasing hormone; and eight patients were given injections of the sustained-release formulation at 2-week intervals over a 6-month period and basal plasma GH levels and the GH response to both an oral glucose load and to thyrotrophin-releasing hormone was assessed. Following a single intramulscular dose of the sustained-release preparation, random GH levels were reduced to below 10 mU/l in five patients and by greater than 50% of basal levels in the remainder. The insulin-like growth factor I (IGF-I) levels fell to within the normal range in three patients. In the long-term efficacy study, GH levels were reduced to < 10 mU/l in 7/8 patients. The IGF-I levels were normalized in four patients. Five of the eight patients experienced diarrhoea, two of mild and three of moderate severity; none of the patients withdrew from the study. Somatuline has been shown to be effective in the treatment of acromegaly. In its sustained-release formulation it clearly represents a useful therapeutic advance, although at the dosage and frequency of injection used in the current protocols it did not provide optimum GH suppression in all patients. MR Johnson, Department of Medicine, Bristol Royal Infirmary, Upper Maudlin Road, Bristol BS2 8HW, UK

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