PROGESTATIONAL ACTIVITY OF STEREOISOMERIC PROGESTERONE-ANALOGUES FOLLOWING ORAL ADMINISTRATION IN AMENORRHOEA

1960 ◽  
Vol XXXV (II) ◽  
pp. 197-203 ◽  
Author(s):  
K.-G. Tillinger ◽  
E. Diczfalusy
Keyword(s):  
Side Effects ◽  
Oral Administration ◽  
Human Subject ◽  
Histological Appearance ◽  
Orally Active ◽  
Progesterone Analogues

ABSTRACT A stereoisomeric analogue of progesterone, 9β,10α-pregn-4-ene-3,20-dione (retro-progesterone) and a 6-dehydro derivative, 9β,10α-pregna-4,6-diene-3,20-dione (6-dehydro-retro-progesterone) were studied for their progestational activity in 26 artificial cycles induced in 17 amenorrhoic women.1 It was found that 6-dehydro-retro-progesterone is a highly potent orally active progestational agent in the human subject. Daily doses of 10 mg of this compound given orally for 10 days induced a definite secretory transformation of the endometrium. The histological appearance of the endometrium following treatment with this compound could not be distinguished from that seen in normal cycles. Both compounds studied were excellently tolerated; no toxic side-effects were observed.

Treatment of human hyperprolactinaemia with a new dopamine agonist: CU 32085 (mesulergin)

1985 ◽  
Vol 110 (4) ◽  
pp. 433-439 ◽  
Author(s):  
D. Dewailly ◽  
P. Thomas ◽  
J. Buvat ◽  
J. L. Wemeau ◽  
J. C. Fourlinnie ◽  
...  
Keyword(s):  
Side Effects ◽  
Oral Administration ◽  
Dopamine Agonist ◽  
Histological Examination ◽  
Suppressive Effect ◽  
Normal Range ◽  
Tumour Shrinkage ◽  
Dose Dependent

Abstract. CU 38085 (mesulergin) was given at doses ranging from 0.5 to 5 mg/day to 37 patients with pathological hyperprolactinaemia of varying aetiology. The effectiveness of this drug on the suppression of hyperprolactinaemia and on the recovery of gonadal functions was equivalent to that of bromocriptine previously given to a different group of 83 hyperprolactinaemic patients. Tumour shrinkage during treatment with CU 32085 was ascertained in two cases of macroprolactinoma. Histological examination after adenomectomy revealed extensive peri-vascular fibrosis in both cases. In most patients, the efficient doses of CU 32085 were 5-fold lower than those of bromocriptine. After acute oral administration in 10 previously untreated patients, 0.5 mg of CU 32085 had a more prolonged suppressive effect on Prl levels than 2.5 mg of bromocriptine (approximately 18 vs 12 h). According to this, 0.5 mg CU 32085 once a day was sufficient to maintain Prl levels within the normal range in 16 patients. Side-effects were similar in nature and frequency to those induced by bromocriptine and seemed to be dose-dependent. They can be avoided by slowly increases of dose at initiation of treatment.

Evaluation of 11β-HSD activities in vivo following oral administration of cortisol-13C4,2H1 to a human subject

Steroids ◽  
2003 ◽  
Vol 68 (2) ◽  
pp. 167-176 ◽  
Author(s):  
Yasuji Kasuya ◽  
Akitomo Yokokawa ◽  
Shinji Takayama ◽  
Hiromi Shibasaki ◽  
Takashi Furuta
Keyword(s):  
Oral Administration ◽  
Human Subject

Topical anesthetics and analgesics

2021 ◽  
pp. 494-500
Author(s):  
William T. Zempsky
Keyword(s):  
Neuropathic Pain ◽  
Side Effects ◽  
Oral Administration ◽  
Topical Administration ◽  
Venous Access ◽  
Clinical Situation ◽  
Chronic Musculoskeletal Pain ◽  
Topical Anesthetics ◽  
Systemic Side Effects ◽  
Inflammatory Drugs

Topical administration of anesthetics and analgesics can allow for the efficient, painless delivery of medications that may reduce systemic side effects associated with the medication, whilst providing clinical advantages over injected or oral administration for the same clinical situation. Topical anesthetics have become widely used prior to a variety of painful procedures in children, including venous access, laceration repair, and injections. Topical administration of nonsteroidal anti-inflammatory drugs, lidocaine, capsaicin, and other agents also are useful for a range of conditions, including acute and chronic musculoskeletal pain, and neuropathic pain.

scholarly journals Intrathecal Riluzole for the Treatment of Patients With Amyotrophic Lateral Sclerosis

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Nicholas M Boulis
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Side Effects ◽  
Oral Administration ◽  
Oral Therapy ◽  
Drug Exposure ◽  
Oral Treatment ◽  
Oral Drug ◽  
Systemic Drug Exposure ◽  
Lateral Sclerosis ◽  
Systemic Drug

Abstract INTRODUCTION Oral riluzole is the only approved treatment known to improve survival in patients with amyotrophic lateral sclerosis (ALS), with modest efficacy and dosing limited by hepatic toxicity and asthenia. We postulated that a continuous intrathecal (IT) delivery of low daily doses of riluzole could elevate spinal cord (SC) concentrations well above those achievable with oral treatment alone, without increasing side-effects. METHODS A 6-wk and a 24-wk GLP study were conducted to evaluate the safety of IT riluzole in purpose-bred hound dogs. Oral riluzole, equivalent to 50 mg BID in humans, was administered in combination with one of 3 IT doses given through continuous infusion. Plasma, SC, and brain concentrations of riluzole were measured, along with assessments of safety and tolerability. RESULTS In the 6-wk study, when combining the oral and IT routes, IT infusion significantly increased SC concentrations well above those achieved with oral drug administration alone, without increasing brain concentrations. All IT doses in combination with oral administration were well tolerated by the animals. In the 6-mo study, the lowest dose used in the 6-wk study was dropped and a higher dose was added. This highest dose of IT riluzole was not tolerated by the dogs and yielded SC and brain concentrations significantly higher than achieved in any of our previous studies. CONCLUSION Continuous IT administration of riluzole when combined with oral administration can increase the SC concentration of riluzole above those achievable with oral therapy, without increasing the risk for adverse events associated with systemic drug exposure or off-target side-effects in the brain. Therefore, IT riluzole infusion when used in conjunction with oral therapy may safely enhance lower motor neuron neuroprotection and improve the survival benefit of the drug through enhanced SC delivery, and, with a careful selection of IT doses, it could be implemented in patients with ALS.

P4481NI956/QGC006, a potent orally active, brain-penetrating aminopeptidase A inhibitor prodrug for treating hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Keck ◽  
H De Almeida ◽  
D Compere ◽  
N Inguimbert ◽  
A Flahault ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Oral Administration ◽  
Sulfonic Acid ◽  
Plasma Sodium ◽  
High Dose ◽  
Hypertensive Rats ◽  
Arterial Blood ◽  
Angiotensin Iii ◽  
Aminopeptidase A ◽  
Orally Active

Abstract Background Brain renin-angiotensin system hyperactivity has been implicated in the development and maintenance of hypertension. We previously showed that aminopeptidase A (APA) generates in the brain, angiotensin III, which exerts a tonic stimulatory control over blood pressure in hypertensive rats. Thus, the central injection of the specific and selective APA inhibitor, EC33 ((3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid), by blocking the formation of brain angiotensin III, normalizes blood pressure in experimental models of hypertension. Therefore, brain APA appears as a potential new therapeutic target for the treatment of hypertension. We then developed RB150/firibastat, a prodrug of EC33, able of inhibiting brain APA activity and decreasing blood pressure in hypertensive rats after oral administration. Purpose However, considering the high dose of orally active RB150/firibastat required to decrease BP in spontaneously hypertensive rats (SHR) (150 mg/kg) and deoxycorticosterone acetate-salt (DOCA-salt) (50 mg/kg) rats, the aim of our work was to develop new more potent APA inhibitor prodrugs with greater bioavailability for inhibiting brain APA activity. Methods We used a salt- and volume-dependent model of hypertension, the DOCA-salt rat. For in vivo assessments of brain APA activity, brains were collected 4 hours after the oral administration. A catheter was inserted into the right femoral artery to monitor mean arterial blood pressure in alert rats. We evaluated plasma arginine-vasopressin (AVP) levels by radioimmunoassay. Rats were individually housed in metabolic cages for urine and electrolyte output measurements. Results We report here the development of a new APA inhibitor prodrug, NI956/QGC006, obtained by the disulfide bridge-mediated dimerization of NI929 ((3S,4S)-3-amino-4-mercapto-6-phenyl-hexane-1-sulfonic acid). NI929 is 10 more efficient than EC33 at inhibiting recombinant mouse APA activity in vitro. Following oral administration at a dose of 4 mg/kg in conscious DOCA-salt rats, NI956/QGC006 normalized brain APA activity and induced a marked decrease in blood pressure of −44±13 mmHg four hours after treatment (p<0.001), sustained over ten hours (−21±12 mmHg, p<0.05). Moreover, NI956/QGC006 decreased plasma AVP levels, and increased diuresis and natriuresis, that may decrease blood pressure by reducing the size of the fluid compartment. Finally, NI956/QGC006 did not affect plasma sodium and potassium concentrations. Conclusions This study shows that NI956/QGC006 is a “best-in-class” central-acting APA inhibitor prodrug, belonging to the same drug class as RB150/firibastat, supporting the strategy of brain APA inhibition for hypertension treatment. Acknowledgement/Funding ANR (Agence Nationale de la Recherche) grant to Catherine Llorens-Cortes (LabCom CARDIOBAPAI) and Quantum Genomics financial support.

scholarly journals Effectiveness of montelukast in childhood asthma: a prospective observational study

2021 ◽  
Vol 8 (3) ◽  
pp. 554
Author(s):  
Krutika Gangdev ◽  
Hemant Jain ◽  
Atul Luhadia
Keyword(s):  
Side Effects ◽  
Inhaled Corticosteroids ◽  
Clinical Symptoms ◽  
Young Patients ◽  
Personal Data ◽  
Major Advance ◽  
Once Daily ◽  
Controller Medication ◽  
Orally Active

Background: Asthma is characterized by hyperresponsiveness of airways to various stimuli, manifested by widespread narrowing of airways causing paroxysmal dyspnoea, wheezing or cough. Most asthma medications are inhalational and compliance is difficult. So, development of an orally active and once daily drug with additional bronchodilator properties would lead to a major advance for managing young patients with asthma.Methods: Children between 6-18 years with not well controlled asthma on daily controller therapy were enrolled. Their personal data and history regarding the duration of asthma symptoms, frequency and severity of exacerbations was noted. Diagnosis and grading of severity of asthma was confirmed by spirometry. Then subjects were started on montelukast as add on to their daily controller therapy and were reassessed at 4, 8 and 12 weeks by clinical symptoms and PEFR. The change in frequency of symptoms and PEFR at the end of 12 weeks gave the outcome of efficacy of montelukast. Side effects of montelukast were also assessed.Results: Among total 64 subjects, at 4 weeks, 52 improved to well-controlled asthma. The remaining 12 did not improve, so required an increase in dose of their daily controller medication. Out of those 12 subjects, 10 subjects improved to well-controlled asthma at 8 weeks and 2 subjects still did not improve, so, their inhaled corticosteroids (ICS) dose was further increased. All 64 subjects showed improvement at 12 weeks. No serious side effects were observed.Conclusions: 81.25% subjects showed improvement at the 1st follow up itself and no serious complications were observed. So, it can be suggested that montelukast is a safe drug.

scholarly journals Simvastatin-induced changes in the leukocytic system of porcine bone marrow

2018 ◽  
Vol 62 (3) ◽  
pp. 329-333 ◽  
Author(s):  
Anna Snarska ◽  
Dominika Wysocka ◽  
Liliana Rytel ◽  
Sławomir Gonkowski ◽  
Hanna Pawelec ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Side Effects ◽  
Oral Administration ◽  
Cholesterol Level ◽  
Muscle Weakness ◽  
Metabolic Pathways ◽  
Bone Marrow Cells ◽  
Mammal Species ◽  
Internal Organs ◽  
Induced Changes

AbstractIntroductionSimvastatin is a substance which is commonly used as a medicine to reduce cholesterol level. Unfortunately, it shows numerous side effects. Simvastatin affects various internal organs, and among other detriments to health may cause persistent muscle weakness, osteolytic processes, headaches, and rashes. Until now knowledge of the influence of simvastatin on bone marrow cells has been rather scant and fragmentary.Material and MethodsDuring this experiment the numbers of all types of cells in the leukocytic system of porcine bone marrow were evaluated after 28 and 56 days of oral administration of simvastatin at a dose of 40 mg/day/animal.ResultsSimvastatin caused an increase in the number of all types of cells in the leukocytic system, and the most visible fluctuations concerned promyelocytes.ConclusionObservations obtained during the present study indicated that the results of the action of simvastatin on porcine bone marrow differ from those observed in other mammal species, including human. This may be due to various metabolic pathways within the bone marrow in the particular species, but the exact mechanisms of these actions are unknown at the present time.

A Double Blind Study of the Effect of Tranexamic Acid in Essential Menorrhagia

1968 ◽  
Vol 20 (03/04) ◽  
pp. 583-587 ◽  
Author(s):  
J Vermylen ◽  
M. L Verhaegen-Declercq ◽  
M Verstraete ◽  
F Fierens
Keyword(s):  
Side Effects ◽  
Oral Administration ◽  
Tranexamic Acid ◽  
Blind Study ◽  
Double Blind Study ◽  
Double Blind

SummaryOral administration of tranexamic acid, in a dosage of 3 g daily from the first day of menstruation onwards, significantly decreases menstrual haemoglobin loss in women with so-called essential menorrhagia.The frequency of side-effects reported did not differ between “active” and “placebo” periods.

The efficacy and the incidence of drowsiness with different modified administrations of olanzapine in preventing chemotherapy induced nausea and vomiting.

2019 ◽  
Vol 37 (31_suppl) ◽  
pp. 121-121
Author(s):  
Yu Qian ◽  
Jun Wang ◽  
Yuan Wu ◽  
Shuang Dong ◽  
Sheng Hu ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Side Effects ◽  
Oral Administration ◽  
Dose Reduction ◽  
Side Effect ◽  
Nausea And Vomiting ◽  
Median Frequency ◽  
Full Dose ◽  
Half Dose ◽  
Delayed Cinv

121 Background: Olanzapine is now widely used for preventing chemotherapy-induced nausea and vomiting (CINV). The recommended oral administration is 10 mg at bedtime. However, drowsiness is one of common side effects of olanzapine. Several modified administrations of olanzapine, such as dose reduction and early taken are being tried in clinical practice to avoid drowsiness. Methods: We retrospectively reviewed 500 patients who used olanzapine for CINV from January 2018 to January 2019 in our department. Eligible criteria include patients who used the constant administration of olanzapine for at least four days to prevent acute and delayed CINV. Patients were grouped into three groups according to three different administrations of olanzapine as full dose (10mg), half dose (5 mg), and early taken (10 mg, six hours before bedtime). Eligible patients were randomly selected in each group as a ratio of 1:1:1. The frequency of CINV, the incidence of drowsiness and the duration of olanzapine administration were collected and compared. Results: There are 267 patients met the criteria and 48 patients in each group. The median frequency of CINV per day in all 144 patients was 3, 1, 1 on day 1 to 3 after chemotherapy respectively. The frequency of CINV was not different among three groups. The incidence of drowsiness was 38%, 20%, and 23% in full dose, half dose and early taken groups (P < 0.05). The median days of administration were 5, 10 and 6 days in full dose, half dose and early taken group, respectively. Conclusions: Modified administration of olanzapine, both by dose reduction and early taken, could have similar effect in preventing CINV but reduced the incidence of the side effect as drowsiness. Further study should be done to explore the proper administration of olanzapine in preventing CINV.

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