The effect of clofibrate with phototherapy in late pre-term newborns with non-hemolytic jaundice.

Background : Despite an understanding of the enzymatic pathways leading to bilirubin production and degradation, very few pharmacologic interventions are utilized and the mainstay of treatment remains phototherapy. Aims : To evaluate the efficacy of clofibrate in reducing total serum bilirubin levels in late pre-term neonates with non-hemolytic jaundice. Design and Setting : Double-blind, placebo-controlled, randomized trial; tertiary level neonatal unit. Materials and Methods : A randomized controlled study was carried out in the neonatal ward of Children's Hospital, Tabriz, Iran, over a 1-year period. Sixty-eight healthy late pre-term infants readmitted with non-hemolytic hyperbilirubinemia were randomized to receive phototherapy and clofibrate (n= 35) or phototherapy and placebo (n= 33). Statistical Analysis Used : Chi-square test and independent sample 't' test. Results : There were no significant differences in the weight, gender, modes of delivery and age of neonates between the two groups. Similarly the mean total serum bilirubin (TSB) level at the time of admission was not significantly different between the two groups [mean± SD: 19.72 ± 1.79 (95% confidence interval: 19.12-20.54 mg/dL) vs. 20.05 ± 2.82 (95% confidence interval, 19.54-22.04 mg/dL), P= 0.57]. The mean TSB 48 hours after phototherapy [mean± SD: 8.06± 1.34 (95% confidence interval: 7.94-10.18 mg/dL) vs.10.94 ± 2.87 (95% confidence interval: 9.92-12.16 mg/dL), P= 0.02] and the mean duration of phototherapy [mean± SD: 64.32 ± 12.48 (95% confidence interval: 60-81.6 hours) vs. 87.84 ± 29.76 (95% confidence interval: 79.2-108 hours), P< 0.001] were significantly lower in the clofibrate-treated group. Conclusions : Clofibrate is an effective adjunctive drug in neonatal hyperbilirubinemia, which results in decreased TSB level and reduced duration of phototherapy in late pre-term newborns.

Efficacy of clofibrate on severe neonatal jaundice associated with glucose-6-phosphate dehydrogenase deficiency (a randomized clinical trial).

Glucose-6-phosphate dehydrogenase (G6PD) deficiency may cause severe hyperbilirubinemia with bilirubin encephalopathy unless intervention is initiated. The aim of this study was to assess the efficacy of clofibrate in full term G6PD deficient neonates with jaundice. A randomized clinical trial study was performed in two groups of full-term G6PD deficient jaundiced neonates (clofibrate treated group, n = 21; control group, n = 19). Infants in the clofibrate group received a single oral dose of 100 mg/kg clofibrate, whereas control group received nothing. Both groups were treated with phototherapy. Serum total and direct bilirubin levels were measured at the onset of treatments, 16, 24 and 48 hours later. On enrollment, the mean total serum bilirubin (TSB) level in the clofibrate treated group was 18.40 +/- 2.41 and in the control group was 17.49 +/- 1.03 (p = 0.401). At 16, 24 and 48 hours of treatment, the mean TSB in the clofibrate group were 15.2 +/- 1.9, 12.6 +/- 2.4, and 10.1 +/- 2.4 and in the control group were 16.5 +/- 1.2, 13.3 +/- 2.2 and 11.4 +/- 2.4, respectively (p = 0.047). At 48 hours, 7 (33%) cases in the clofibrate group and one (5%) case in the control group were discharged with a TSB < 10 mg/dl (p = 0.031). No side effects were observed on serial examinations during hospitalization, or on the 1st and 7th days after discharge. The results show that clofibrate induces a faster decline in serum total bilirubin level, a shorter duration of phototherapy, and hospitalization with no side effects in full-term G6PD deficient neonates with jaundice.

Effect of clofibrate in non-hemolytic indirect hyperbiliru-binemia in full term neonates.

OBJECTIVE: Jaundice is a common clinical problem in neonatal period which may result in brain damage even in healthy full term newborns, when it is severe. The aim of this study was to characterize the therapeutic effect of clofibrate in full term neonates who present with nonhemolytic jaundice. METHODS: A clinical controlled study was performed on 60 full term neonates who presented with non- hemolytic jaundice. 30 neonates were treated with a single oral dose of clofibrate (100 mg/Kg) plus phototherapy (case group), while 30 neonates received only phototherapy (control group). Both groups were compared in regard to post therapeutic mean total and indirect plasma bilirubin levels, admission duration and the rate of exchange transfusion. RESULTS: The reduction rate of total and indirect plasma bilirubin levels were significantly higher in the clofibrate- treated group as compared with the control group (P< 0.05). The mean duration of admission was found to be reduced from 2.9 +/- 0.9 days in the control groupl to 2.2 +/- 0.6 days in clofibrate- treated group (P=0.002). The mean plasma total bilirubin level was lower in the clofibrate- treated group. No cases required phototherapy after 48 hour in clofibrate- treated group, while 9 neonates (30%) and 2 neonates (6.7%) required phototherapy after 72 hour and 96 hour respectively in the control group. There was no difference between both the groups for sex, the time of developing jaundice and the rate of exchange transfusion. CONCLUSION: A single dose of clofibrate (100 mg/Kg) along with phototherapy is more effective than phototherapy alone in treating non-hemolytic hyperbilirubinemia in term healthy newborn infants.

Terapia hipolipemiante em situações especiais: hipotireoidismo e hepatopatias / Hypolipidemic therapy in special situations: hypothyroidism and liver disease

O hipotireoidismo é comum entre pessoas idosas, especialmente entre as mulheres. A suspeita diagnóstica deve se basear na presença de sinais e sintomas clássicos e a detecção pode ser feita pela elevação dos níveis do hormônio tireo-estimulante (TSH). Anormalidades lipídicas na presença de hipotireoidismo sub-clínico são de menor impacto. Entretanto, a reposição específica de hormônio tireoideano é tão mais importante quanto a magnitude do distúrbio glandular. Na vigência de doença hepática, alguns agentes hipolipemiantes podem levar a um agravamento do quadro, entretanto, estudos recentes têm mostrado que as estatinas podem ser utilizadas na presença de esteatose hepática. Terapia hipolipemiante combinada pode induzir aumentos de enzimas hepáticas e o monitoramento cuidadoso é recomendado nestes pacientes.

Effect of clofibrate in jaundiced term newborns.

OBJECTIVE: Clofibrate is a glucuronosyl transferase inducer that has been proposed to increase the elimination of bilirubin in neonates with hyperbilirubinemia. The aim of this study was to characterize the therapeutic effect of clofibrate in neonates born at full term and present with non-hemolytic jaundice. METHODS: A clinical controlled study was performed in two groups of healthy full term neonates. Thirty neonates were treated with a single oral dose of clofibrate (100 mg/kg) plus phototherapy (clofibrate-treated group) while another 30 neonates (control group) received only phototherapy. RESULT: The mean plasma total bilirubin levels of 12th, 24th and 48th hours were significantly lower in the clofibrate-treated group as compared with the control group (P < 0.0001, P < 0.0001 and P = 0.004, respectively). Treatment with clofibrate also resulted in a shorter duration of jaundice and a decreased use of phototherapy (P < 0.0001). No side effects were observed. CONCLUSION: Although other pharmacological agents such as metalloporphyrins and Sn-mesoporphyrin also seem to be effective in decreasing bilirubin production, these products are not available for routine use and cannot be used because the safety of these drugs has to be confirmed prior to their widespread use. Therefore, clofibrate is now the only available pharmacological treatment of neonatal jaundice.

Iatrogenia: a importância do diagnóstico clínico; miopatia induzida por clofibrate / Iatrogeny: the importance of clinical diagnosis; myopathies induced by clofibrate

Os autores descrevem o caso de uma enferma que apresentou síndrome polimiosite símile durante tratamento de hipercolesterolemia com clofibrate. Com a suspensäo da medicaçäo, os sinais e sintomas de acometimento muscular desapareceram por completo. Os autores chamam a atençäo para a importância das miopatias iatrogênicas no diagnóstico diferencial de pacientes com doenças do sistema neuromuscular

Dissolution of gall-stones in vitro.

An in vitro study on dissolution of 36 gall-stones obtained from 3 patients (12 stones from each patient) was carried out in heparin, bile salt and clofibrate solutions of different strengths. Heparin was found to be a poor solvent while bile salt (sodium desoxycholate) proved better and clofibrate the best solvent in various concentrations used. In addition 3 stones, one from each patient, were placed in normal saline to serve as control.

Clinical trials with gugulipid. A new hypolipidaemic agent.

Multicentric clinical trials of the efficacy of gugulipid conducted at Bombay, Bangalore, Delhi, Jaipur, Lucknow, Nagpur and Varanasi have been reported. Two hundred and five patients completed 12 week open trial with gugulipid in a dose of 500 mg tds after 8 week diet and placebo therapy. One patient showed gastrointestinal symptoms which did not necessitate withdrawal of the drug. A significant lowering of serum cholesterol (av. 23.6%) and serum triglycerides (av. 22.6%) was observed in 70-80% patients Double-blind, crossover study was completed in 125 patients with gugulipid therapy and in 108 patients with clofibrate therapy. Two patients had flu-like syndrome with clofibrate and opted out from the study. With gugulipid the average fall in serum cholesterol and triglycerides was 11 and 16.8% respectively and with clofibrate 10 and 21.6% respectively. The lipid lowering effect of both drugs became evident 3-4 week after starting the drug and had no relationship with age, sex, and concomitant drug intake. Hypercholesterolaemic patients responded better to gugulipid therapy than hypertriglyceridaemic patients who responded better to clofibrate therapy. In mixed hyperlipidaemic patients response to both drugs was comparable. HDL-cholesterol was increased in 60% cases who responded to gugulipid therapy. Clofibrate had no effect on HDL-cholesterol. A significant decrease in LDL-cholesterol was observed in the responder group to both drugs.

Effectiveness of N-N-bis-P-chlorophenyl-3p-tolyl glutaric acid diamide (SRC-3605) as a hypocholesterolaemic compound in hypercholesterolaemic female weanling and adult rats.

SRC-3605, N-N-bis-P-chlorophenyl 3-p-tolyl glutaric acid diamide, was studied for its hypocholesterolaemic effect on serum and liver cholesterol in hypercholesterolaemic weanling and adult female rats. Weanlings were administered doses of SRC-3605 ranging from 100 to 300 mg/kg body weight for 4 or 8 consecutive days. The greatest hypocholesterolaemic effect was observed with doses of 150, 200 and 250 mg, although a progressive decreases in serum cholesterol was noted with increasing doses. Hepatic cholesterol decreases supported the serum data, but were inconsistent. Hypercholesterolaemic adult animals received 50, 100, 150 or 200 mg/kg body weight of either SRC-3605 or clofibrinic acid for 4 days. A decrease in serum cholesterol levels was observed only with the 200 mg SRC-3605. No clear-cut influence of the either compounds was found on hepatic cholesterol. The results indicated that SRC-3605 possesses the property to reduce both serum and liver cholesterol in hypocholesterolaemic weanling female rats.