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PubMed1997

Antenatal betamethasone therapy augments isoproterenol and prostaglandin E2-mediated relaxation of preterm ovine pulmonary veins.

Antenatal glucocorticoid therapy improves pulmonary function in preterm newborns. We have determined the effect of antenatal glucocorticoid therapy on isoproterenol and prostaglandin (PG) E2-mediated relaxation in preterm ovine pulmonary veins after birth. Ovine fetuses (121 and 126 d of gestation; term = 150 d) received an ultrasound guided intramuscular injection of betamethasone, 0.5 mg/kg, or saline. Lambs were delivered 15 or 48 h later, ventilated for 3 h, and killed. Isolated fourth generation pulmonary veins were suspended in organ chambers filled with modified Krebs-Ringer solution (95% O2, 5% CO2) at 37 degrees C, and their isometric tension was recorded. During contractions to U46619, isoproterenol and PGE2 induced greater relaxations of pulmonary veins of betamethasone-treated lambs than those of control. Forskolin, an activator of adenylate cyclase, caused greater relaxation in veins of betamethasone-treated lambs than in those of controls. A greater relaxation of veins treated with betamethasone than that of control veins also occurred in the presence of isobutylmethylxanthine, an inhibitor of phosphodiesterases. All vessels relaxed similarly to 8-bromo-cAMP, a cell membrane-permeable analog of cAMP. When stimulated with isoproterenol, PGE2, and forskolin, adenylate cyclase activity of crude membrane preparations of pulmonary veins treated with betamethasone was greater than that of controls. These results demonstrate that antenatal betamethasone therapy potentiates isoproterenol and PGE2-mediated relaxation of pulmonary veins of preterm lambs; an enhanced adenylate cyclase activity explain in part the effect of antenatal glucocorticoid therapy on pulmonary veins of preterm lambs.

Adenylyl Cyclases↗
PubMed2004

Antenatal betamethasone changes cord blood monocyte responses to endotoxin in preterm lambs.

Corticosteroids are routinely administered to women at risk for preterm delivery to induce fetal lung maturation. Antenatal corticosteroids have immunomodulatory effects on fetal immune cells that are poorly understood. We hypothesized that maternal betamethasone would alter in fetal monocytes both the initiation of inflammation in response to pro-inflammatory stimuli and the resolution of inflammation by phagocytosis of apoptotic neutrophils. Preterm lambs at 124 d gestation were delivered 15 h, 1 d, 2 d, or 7 d after 0.5 mg/kg maternal intramuscular betamethasone. Monocytes from cord blood were isolated and cultured and results were compared with monocytes from preterm lambs exposed to maternal saline or monocytes from adult sheep. Phagocytosis of Escherichia coli was not changed, however, phagocytosis of apoptotic neutrophils was low in fetal monocytes but increased after 7 d exposure to maternal betamethasone to the level found in adult monocytes. Hydrogen peroxide production after endotoxin stimulus was significantly reduced to 7.1 +/- 2.2 micromol at 5 h, 8.7 +/- 2.9 micromol at 24 h, and 4.1 +/- 1.9 micromol at 48 h versus 16.4 +/- 3.6 micromol in control animals; at 7 d, the hydrogen peroxide production increased to 74.3 +/- 19.7 micromol (p < 0.05, per 10(6) monocytes). IL-6 production was reduced at 15 h after maternal betamethasone but at no other time point. Maternal betamethasone initially suppressed several fetal monocyte functions, however, at 7 d, measurements of initiation and resolution of inflammation were increased to levels similar to monocytes from adult sheep. The time-dependent changes in maternal betamethasone modulation of the responses of fetal monocytes may influence immune function of the preterm lamb after delivery.

Adrenal Cortex Hormones↗
PubMed2004

Effects of antenatal betamethasone administration on fetal heart rate and behavior in twin pregnancy.

The efficacy of antenatal corticosteroid therapy in reducing the incidence of respiratory distress syndrome in twin pregnancy is controversial. The corticosteroid levels achieved with the current regimen might not be high enough to reach both siblings. In singleton fetuses, maternal betamethasone administration causes transient reductions in fetal heart rate (FHR), FHR variability, and body and breathing movements. We performed a prospective study to determine whether there are similar effects of betamethasone on FHR and behavior in preterm twin pregnancy and whether the effects occur similarly in both twin members. Eighteen women who were carrying twins received optimal corticosteroid treatment. Simultaneous recordings were made on twins before (day 0), during (days 1-2), and after (days 3-4) corticosteroid therapy using separate cardiotocography and ultrasound machines. Betamethasone administration was associated with significant transient decreases in basal FHR (day 1), FHR variability (days 2 and 3), and body and breathing movements (day 2). The overall changes in twins were similar to those previously found in singleton pregnancies. There was a high degree of association of response to betamethasone among individual members of twin pairs. The betamethasone-induced effects were unrelated to fetal sex, positioning, chorionicity, and discordance in size, but there was an effect of gestation on FHR. We conclude that the current regimen of antenatal corticosteroids used in preterm twin pregnancies results in observable physiologic and behavioral changes in twin pairs irrespective of their composition. This provides evidence that the achieved betamethasone levels are high enough to reach the compartment of either twin member.

Adult↗
PubMed1991

Pretreatment with betamethasone of patients with Graves' disease given radioiodine therapy: thyroid autoantibody responses and outcome of therapy.

The effects of betamethasone on thyroid autoantibody responses and outcome of radioiodine therapy were determined over a period of 1 yr in a prospective randomized study of 40 patients with Graves' disease. Twenty patients were given placebo tablets, and 20 patients were treated with beta-methasone from 3 weeks before until 4 weeks after 131I therapy. At the time of inclusion in the study, the mean serum concentrations of TSH receptor antibodies, thyroid peroxidase antibodies, and thyroglobulin antibodies (TgAb) were increased in both groups. Three weeks of treatment with betamethasone reduced the thyroid peroxidase antibody and TgAb titers as well as the serum concentrations of thyroid hormones. A decrease in the TSH receptor antibody level was not statistically significant. After radioiodine therapy, transient increases in thyroid autoantibody levels were observed. The titers of the different antibodies generally changed in parallel. In some patients a detectable level of a given antibody was found only after the radioiodine treatment, and in two cases, TgAb did not appear at all, although the two other antibodies increased temporarily. Betamethasone delayed, but did not abolish, the 131I-induced antibody peaks. Betamethasone also caused a reduction in the total serum immunoglobulin G, a reduction which persisted throughout the study period. When the study ended, 17 patients given placebo and 9 patients given betamethasone (P less than 0.001) were receiving replacement therapy due to the development of hypothyroidism. These patients at this point in time had lower antibody levels than those not requiring T4. The results of this study demonstrate that betamethasone reduces and modifies the thyroid autoantibody responses as well as the outcome of radioiodine therapy in patients with Graves' disease. From a clinical point of view, these effects may be in opposite directions.

Aged↗
PubMed2002

The effect of betamethasone administration to pregnant women on maternal serum indicators of infection.

OBJECTIVE: To study the effect of betamethasone therapy on maternal white blood cell count, C-reactive protein and erythrocyte sedimentation rate in women at high risk for preterm delivery. STUDY DESIGN: We included women at gestational age of 24 to 34 weeks who were treated by betamethasone for enhancement of fetal lung maturity, because of imminent preterm labor with intact membranes. Blood tests for white blood cell and differential count, C-reactive protein and erythrocyte sedimentation rate were drawn before betamethasone injection, 2 hours after, and then every 24 hours for three days. RESULTS: 105 women were included. The mean white blood cell count increased by 33% on day one, and returned to baseline level three days after the first injection of betamethasone. A significant rise in neutrophil count, and drop in lymphocyte count was noted as early as two hours after the first injection and lasted for two days. Mean C-reactive protein and erythrocyte sedimentation rate levels were not changed significantly by betamethasone treatment. CONCLUSIONS: Antenatal betamethasone therapy causes a transient increase in maternal leukocyte count but has no effect on serum C-reactive protein and erythrocyte sedimentation rate. This information is relevant for preterm pregnant women who are at high risk for chorioamnionitis.

Adult↗
PubMed1996

Prenatal effects of betamethasone-L-carnitine combinations on fetal rat lung.

Lungs of fetal rats between the 18th and 20th gestational day (total gestation lasting 22 days) were examined. There was a significant increase (p < 0.01) of the dipalmitoyl phosphatidylcholine content from day 19 to day 20 of gestation. In the second trial, pregnant rats were treated with different doses of betamethasone, L-carnitine, betamethasone-L-carnitine combinations, and saline (controls) for three days before Cesarean section on the 19th gestational day. Maternal injections of 0.10 mg/kg body weight betamethasone and 100 mg/kg body weight L-carnitine significantly (p < 0.05, p < 0.01 respectively) increased the dipalmitoyl phosphatidylcholine content of fetal lungs. Combinations of either 0.05 or 0.10 mg/kg body weight betamethasone with 100 mg L-carnitine also significantly increased the dipalmitoyl phosphatidylcholine content of the fetal lungs above control values (p < 0.001) and values achieved with betamethasone alone (p < 0.05). Maternal treatment with a betamethasone-L-carnitine combination on day 19 of gestation resulted in dipalmitoyl phosphatidylcholine levels comparable to those found on the 20th gestational day during normal lung maturation. Fetal rats delivered on the 20th gestational day survived, while fetuses delivered on the 19th gestational day did not survive.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1988

Betamethasone-dixyrazine versus metoclopramide as antiemetic treatment in cancer chemotherapy.

In a prospective randomized and double-blind cross-over study betamethasone-dixyrazine was compared with metoclopramide as antiemetic treatment in cisplatin and doxorubicin chemotherapy. Sixty-two consecutive patients without prior experience of chemotherapy entered the study and were followed during 1-4 courses of treatment. Effect parameters were recorded on questionnaires using the visual analog scale for quantification. The median number of courses per patient was 3.0 (range 1-4). Full protection against nausea and vomiting was achieved in 74% with betamethasone-dixyrazine and in 45% with metoclopramide regardless of the chemotherapy regimen employed. With doxorubicin regimens betamethasone-dixyrazine gave full protection in 94% and metoclopramide in 45%. In cisplatin regimens full emetic protection was achieved in 40% with betamethasone-dixyrazine and in 29% with metoclopramide. Adverse reactions were a significant problem with metoclopramide: restlessness 48%, akathisia 26%, parkinsonism 13%, and acute dystonia 3%. One case (3.2%) of parkinsonism was noted as the only extrapyramidal reaction in the dixyrazine group. Various degrees of sedation were noted in 84% during dixyrazine treatment compared with 71% during metoclopramide therapy. Diarrhea was encountered in 48% after high-dose metoclopramide compared with 6% after antiemetic treatment with betamethasone-dixyrazine. Betamethasone-dixyrazine appears to be a promising antiemetic combination with regard to both efficacy and side effects, but further refinement of the regimen is probably possible through dose adjustments and alternative routes of administration.

Antiemetics↗
PubMed2001

[Treatment of phimosis with betamethasone ointment in children].

OBJECTIVE: We evaluated the efficacy of betamethasone ointment in the treatment of childhood phimosis and determined the most effective concentration of betamethasone. MATERIAL AND METHODS: Between August 1996 and May 2000, 69 patients (median age 3.0, range 0-12) presented to our department with severe phimosis (grade 4, Tsugaya's classification), and were enrolled in this study and treated with betamethasone ointment for 4 weeks. The ointment was applied on the narrowed preputial skin twice a day by parents. During the first week, parents were asked not to retract the foreskin. After this period, parents were encouraged to retract the foreskin gently and without intense tension. The concentration of betamethasone were 0.12%, 0.05% and 0.025%. If the patients become to be able to retract foreskin satisfactory, we consider the state as complete response. If he become to be able to retract to allow partial exposure of the glans, we consider the state as partial response. We compared the efficacy among each of the concentrations, and at 3 months after the end of the treatment, we also assessed the adverse effects and recurrence. RESULTS: The overall success rate was 85.5%. Success rates with 0.12%, 0.05% and 0.025% ointment were 96.8%, 82.8% and 55.6%, respectively (p = 0.0001). The 0.12% ointment was most effective. Recurrence was observed in 3 patients (4.3%). No adverse effects were observed in any of the patients. CONCLUSIONS: Treatment with betamethasone ointment is very effective, easy and safe. We recommend betamethasone ointment as the first treatment of choice for childhood phimosis.

Betamethasone↗
PubMed1999

Betamethasone prevents virus-induced airway inflammation but not airway hyperresponsiveness in guinea pigs.

In this study the effect of betamethasone was investigated in guinea pigs that demonstrate airway inflammation and airway hyperresponsiveness after a viral respiratory tract infection with parainfluenza-3 (PI3) virus. Guinea pigs were pretreated with saline or betamethasone 8 mg/kg intraperitoneally twice a day for five consecutive days, starting on day 0 and ending on day 4. On day 1, the guinea pigs were inoculated with either control solution (medium) or PI3 virus. On day 5, airway responsiveness was measured. Furthermore, a blood sample was taken, lungs were lavaged, blood leucocytes were counted, and bronchoalveolar lavage (BAL) cells were counted and differentiated. Accordingly, the activity of the bronchoalveolar cells was measured by lucigenin-amplified chemiluminescence. In virus-infected guinea pigs the total bronchoalveolar cell number was increased by 44% compared with medium-treated guinea pigs. This was mainly due to the increase in macrophages (70%, P < 0.05) and eosinophils (344%, P < 0.001). The increase in both total and differential (macrophages and eosinophils) cell numbers in virus-infected guinea pigs was completely abolished in animals treated with betamethasone. Moreover, betamethasone prevented the decrease in number of blood leucocytes in virus-infected guinea pigs. In contrast, betamethasone did not prevent the increase in airway responsiveness to both histamine (>200%) and methacholine (>100%) after the virus infection. In conclusion, betamethasone treatment prevents virus-induced airway inflammation but not airway hyperresponsiveness in guinea pigs.

Animals↗
PubMed1975

[First experiences with prenatal affection of infantile lung maturation by betamethason (author's transl)].

Because of premature labour, probability of fetal retardation, discrepance at term of delivery, Rh-incompatibility or EPH-gestosis 185 patients were hospitalized. 76 pregnant women received twice 1.5 ml Celestan Depot i.m. (4.5 betamethasone acetate and 6mg betamethasome dinatrium phosphate per injection) within an interval of 24 hours. It was necessary to maintain a tocolysis for at least 48 hours as a minimum after the first injection of Celestan Depot. The other 109 patients without treatment of glucocorticoids were considered as a controlgroup. We could show that antepartum application of betamethasone before the 38. week of gestation was associated with a reduction of RDS in our premature infants. Only one baby of the betamethasone-treated infants died of hyaline membrane disease during the first 7 days of life compared with 11 of the control group. In 11 patients patients amniocentesis was performed before the first injection of glucocorticoids and was repeated 2 to 7 days later. The amniotid fluid lecithin phosphorus concentration was determined. In the same period of pregnancy and the same iterval the lecithin phosphours level of amniotic fluid was analysed in 11 other patients who were not rreated with glucocorticoids. The difference between amniotic fluid lecithin phosphorus concentration in the first and second anslysis was found significant by a level of significance of alpha = 5%. There was no evidence of an influence of the therapy with Celestan Depot on this increase. The excretion of oestorgens in the urine of 24 hours was analysed in 22 gradidae before and 7 days after the treatment with betamethasone. The oestogen values of the day before application of betamethasone served as baseline figures. All patients showed a market fall in urinary oestrogens excretion, especially after the second day of therapy. After day 2 the values returned rapidly to baseline values. There were no differences between treated and control groups in Apgar scores at birth or in the incidence of icterus neonatroum (bilirubine level is greater that 10 mg% in the serum). The results of our study support the hypothesis that in humans glucocorticoid administration to the fetus accelerates lung maturation. Relatively brief intrauterine exposure of human infants to pharmacological doses of betamethasone was associated with a substantial reduction in the incidense of RDS.

Amniotic Fluid↗
PubMed1980

[Pituitary adrenocortical response to high dose administration of betamethasone in neurosurgical patients (author's transl)].

Using RIA technique, response patterns of ACTH-adrenocortical system to short term large dose corticosteroid therapy for neurosurgical patients were investigated. The subjects were consisted of 20 males and 13 females, ageing ranging from 10 to 60 years old. The subjects were divided into three groups according to mode of steroid administration. In the first group, 12 mg/day of betamethasone were administered for 5 days and cancelled without gradual reduction. In the second group, 12 mg/day of betamethasone were administered for 4 days and 6 mg/day of betamethasone were given for following 2 days. In the third group, 12 mg/day of betamethasone were administered for 3 days and gradual reduction of betamethasone was given for following 4-5 days. Response of plasma cortisol level to synthetic 18-ACTH were measured in all patients for 3 days after betamethasone administration cancelled. The results led to the following conclusion. 1) The second and third groups had not any clinical symptom after steroid cancelled, but one half cases of the first group had mild headache, nausea for 2 days after cancelled. 2) Recovery process of adrenocortical function in the second group is most rapidly, compared with that in other two groups. 3) In the postoperative steroid therapy in neurosurgery, it could be concluded that 4 days massive administration of steroid followed by stepwise reduction in 2 days would be functionally well tolerated by adrenocortical system.

Adolescent↗
PubMed1983

Betamethasone-mediated activation of biphenyl 2-hydroxylation in rat liver microsomes. Studies on possible mechanisms.

The addition of the steroid betamethasone to intact or detergent-solubilized rat liver microsomes caused a concentration-dependent increase in the rate of biphenyl 2-hydroxylation. Betamethasone (100 microM) increased the apparent Vmax for 2-hydroxybiphenyl formation 2- to 4-fold but had no effect on the apparent Km when either the biphenyl or NADPH concentration was varied. Betamethasone had little or no effect on the apparent Vmax or apparent Km of the 3- and 4-hydroxylations of biphenyl. The steroid did not enhance biphenyl 2-hydroxylation through a peroxidative mechanism. Betamethasone had little or no effect on the rate of the NADPH-dependent reduction of cytochrome c or total microsomal cytochrome P-450. The addition of purified NADPH-cytochrome P-450 reductase to cholate-solubilized liver microsomes increased the rate of hydroxylation of biphenyl in positions 2 and 4. Betamethasone (100 microM) decreased the apparent Km for purified cytochrome P-450 reductase by 48% and increased the apparent Vmax of 2-hydroxybiphenyl formation by 2-fold when the concentration of cytochrome P-450 reductase was varied. The steroid did not alter the Km or Vmax values for the 4-hydroxylation of biphenyl. The data suggest that betamethasone enhances the interaction between the reductase and the form(s) of cytochrome P-450 responsible for the 2-hydroxylation of biphenyl.

Animals↗
PubMed1981

[Placental transfer and distribution of betamethasone 17,21-dipropionate in various regions of the brain of pregnant rats and mice (author's transl)].

As betamethasone 17,21-dipropionate induces adrenal atrophy in rat dams and adrenal hypertrophy in the fetus, we investigated the placental transfer of this compound using autoradiography and liquid scintillation counting in animals in the late stages of pregnancy. In these two species, 3H-betamethasone 17,21-dipropionate and/or its metabolites transferred across the placental barrier into fetal tissues and were distributed at levels lower than detected in the maternal tissues. The rat fetus showed a high uptake of radioactivity in the adrenal cortex. In pregnant rats, the ratios of the radioactivity in the adrenal cortex. In pregnant rats, the ratios of the radioactivity in brain tissues to the plasma in fetuses were much higher than in the dams after the administration of 3H-betamethasone 17,21-dipropionate or 3H-betamethasone. In the dams given 3H-betamethasone 17,21-dipropionate, the accumulation of radioactivity in the hypothalamus and septum was significantly greater than in other regions. The present study suggests that betamethasone 17,21-dipropionate or its metabolites transferred across the placental barrier following administration to the mother rat may produce an adrenal hypertrophy in the fetus and that accumulation of radioactivity in the hypothalamus of the dam may be related to a suppression of the function of hypothalamo-pituitary-adrenal axis.

Animals↗
PubMed1995

Comparison of the distinct effects of epidermal growth factor and betamethasone on the morphogenesis of the gas exchange region and differentiation of alveolar type II cells in lungs of fetal rhesus monkeys.

To compare the effects of epidermal growth factor (EGF) and betamethasone on the morphogenesis of the gas exchange region and the differentiation of the alveolar type II cell during fetal lung development, fetal rhesus monkeys (78% gestation) were treated in utero with EGF (5.33 mg/kg total dose), beta-methasone (2.6 mg/kg total dose) or the carrier, saline (control), every other day for 7 days. EGF-treated monkeys had significantly increased body and adrenal weights. Betamethasone-treated monkeys had significantly decreased body and adrenal weights. Exogenous EGF reduced cytoplasmic glycogen and increased the cytoplasmic organelle and SP-A content within alveolar type II cells. In contrast, exogenous betamethasone did not alter alveolar type II cell cytodifferentiation. Neither EGF nor betamethasone treatment significantly altered the structure of the gas exchange region as shown by a lack of change from controls in alveolar airspace size or in the fraction of the gas exchange region that was potential airspace. We conclude that at clinically relevant doses, EGF greatly accelerates the maturation of alveolar type II cells, whereas betamethasone does not. Exogenous EGF may act directly on alveolar type II cells because these cells contain EGF receptor. Neither EGF nor betamethasone had dramatic effects on the morphogenesis of the gas exchange region.

Amniotic Fluid↗
PubMed1994

Maturational response of colonic and renal Na+,K(+)-ATPase activity to K+ load and betamethasone in preterm rats.

Preterm human infants demonstrate high fecal K+/Na+ ratio that is inversely related to maturation. Renal and colonic basolateral membrane-located Na+,K(+)-adenosine triphosphatase (Na+,K(+)-ATPase) governs K+ excretion and is enhanced by both steroid administration and K+ loading. However, the response of premature kidney or colon to these stimuli is not well studied. We measured basal as well as stimulated levels of renal and colonic Na+,K(+)-ATPase activity in response to betamethasone and K+ load given separately and betamethasone given after K+ load in premature, mature, and 4-day-old Sprague-Dawley rats. Although preterm rats showed a higher basal level in the kidneys (p < 0.004), an increase in enzyme activity in response to the stimuli was achieved only in the colon (p < 0.001 for betamethasone, p < 0.0001 for K+ load, and p < 0.0007 for the combination). At term and at 4 days of postnatal age, however, the kidneys showed much higher levels than the colon in response to stimuli (p < 0.0001 for all) except for betamethasone at term. The response of colonic tissue of preterm and term rats to betamethasone given 4 days after a K+ load was less marked than response to betamethasone or K+ load given separately (p < 0.001). The stimulated levels achieved in the preterm colon were higher than the basal preterm renal values (p < 0.001). The tissue K+ content increased in response to K+ load in only the preterm colon (p < 0.05). We have demonstrated a tissue specificity in the development of Na+,K(+)-ATPase activity in K+ excretory organs of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1977

[Prevention of idiopathic respiratory distress syndrome. Influence of betamethasone on the frequency of respiratory distress syndrome in a premature infant collective at the Bonn University Gynecologic Clinic].

Out of a group of 189 pregnant women, who were in the 28th to 37th week of gestation, 57 women received i.m. injections of betamethasone. 132 premature infants whose mothers were not treated served as controls. Betamethasone caused a significant decrease in established respiratory distress syndrome (RDS). In the betamethasone group there was an incidence of 7% of respiratory distress syndrome as compared to 23,5% in the control group. Neonatal mortality was 1,8% in the treated group versus 10,6% in the control group. The occurrence of suspected respiratory distress syndrome also was significantly lowered after betamethasone. In the control group premature rupture of membranes or administration of tocolytic drugs did not have any effect on the frequency of respiratory distress syndrome. However, the premature babies who were delivered by caesarian section had a significantly higher incidence of respiratory distress syndrome than those who were delivered vaginally. After betamethasone treatment the occurrence of respiratory distress syndrome after caesarian section was as low as in the group with vaginal delivery. The present study of a larger group of premature babies has confirmed previous positive results of betamethasone treatment.

Apgar Score↗
PubMed1998

The effect of topical diltiazem on the intraocular pressure in betamethasone-induced ocular hypertensive rabbits.

The effect of calcium channel blockers (CCBs) on intraocular pressure (IOP) remains still controversial, although some preliminary reports suggest that these drugs may be effective in the management of ocular hypertension and low-tension glaucoma. The aim of the present work was to assess the effect of topical diltiazem on IOP in an animal model for glaucoma, the betamethasone-induced ocular hypertension in rabbits. IOP was measured with a manometrically calibrated applanation pneumatonograph. Ocular hypertension was produced in 120 rabbits by weekly subconjunctival injection of a betamethasone suspension into the left eye. The experiments examining the ocular actions of diltiazem were carried out in two stages. In the first one, the ability of topical diltiazem to prevent the rise in IOP induced by betamethasone was studied. In a second phase, the effect of topical diltiazem on IOP in betamethasone-induced ocular hypertensive rabbits was assessed. Diltiazem was topically applied once daily for 5 days a week into the left eye. The effect of five different concentrations of diltiazem was evaluated to obtain dose-response curves. Topical diltiazem was found to prevent in a dose-related fashion the betamethasone-induced IOP rise as well as to reduce IOP in rabbits made ocular hypertensive by weekly subconjunctival injection of betamethasone. Unilateral topical administration did not produce a clear effect on IOP in the untreated eye. This is the first report describing the ocular hypotensive action CCBs in animal model for glaucoma. These findings are in agreement with preliminary evidence suggesting that CCBs may have a beneficial effect in human ocular hypertension.

Administration, Topical↗
PubMed1982

The stability and blanching efficacy of betamethasone-17-valerate in emulsifying ointment.

The bio-availability of betamethasone-17-valerate (Betnovate ointment) in emulsifying ointment (1 in 4 dilution) was investigated in ten subjects using a single-application vasoconstrictor assay; the blanching induced was measured using a skin reflectance spectrophotometer. The vasoconstrictor activity of the diluted preparations decreased with age. There was no significant difference between the vasoconstrictor activity of freshly made Betnovate 1 in 4 in emulsifying ointment and undiluted Betnovate ointment, and between 3-4 week old diluted Betnovate and emulsifying ointment base. Blanching induced by freshly prepared 4, 8 and 16-fold dilutions was not significantly different but a large reduction in blanching occurred on diluting 32-fold with emulsifying ointment. The degradation of betamethasone -17-valerate in emulsifying ointment was quantified by high performance liquid chromatography. More than 60% of the betamethasone -17-valerate underwent degradation within 6 h. There was a simultaneous increase in the concentration of betamethasone-21-valerate which peaked within 2 days and was followed by a slow degradation (half-life 8 days) to betamethasone free alcohol.

Betamethasone↗