Quantitative determination of ademetionine in tablets utilizing ATR-FTIR and partial least squares methods approaches.

In this study there were utilized a combination of Fourier transform infrared spectroscopy in attenuated total reflection mode (ATR-FTIR) and partial least squares (PLS) regression method to develop quantitative models for determining the concentration of ademetionine in commercial tablets. The established and validated models were specifically designed for a commercial product containing ademetionine 1,4-butandiesulfonate. The coefficient of determination for the developed model was 0.999. Relative standard deviation (RSD) does not exceed 1.6% for repeatability and intermediate accuracy, which meets the international ICH and AOAC requirements for the method performance. The validation results effectively confirmed that this method is suitable and meets the current requirements for analytical methods in drug quality control. Consequently, this approach can be used for routine ademetionine analysis in pharmaceutical products and has the potential to be applied to other active pharmaceutical ingredients (APIs) in drug quality control.

Effect of polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine on pregnancy outcomes in intrahepatic cholestasis.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that occurs in pregnant women and can lead to a range of adverse pregnancy outcomes. The condition is typically marked by pruritus (itching) and elevated levels of liver enzymes and bile acids. The standard treatment for ICP has generally been ursodeoxycholic acid and ademetionine 1,4-butanedisulfonate, but the efficacy of this approach remains less than optimal. Recently, polyene phosphatidylcholine has emerged as a promising new therapeutic agent for ICP due to its potential hepatoprotective effects. AIM: To evaluate the effect of polyene phosphatidylcholine/ursodeoxycholic acid/ ademetionine 1,4-butanedisulfonate on bile acid levels, liver enzyme indices, and pregnancy outcomes in patients with ICP. METHODS: From June 2020 to June 2021, 600 patients with ICP who were diagnosed and treated at our hospital were recruited and assigned at a ratio of 1:1 via random-number table method to receive either ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate (control group, n = 300) or polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate (combined group, n = 300). Outcome measures included bile acids levels, liver enzyme indices, and pregnancy outcomes. RESULTS: Prior to treatment, no significant differences were observed between the two groups (P > 0.05). Post-treatment, patients in both groups had significantly lower pruritus scores, but the triple-drug combination group had lower scores than the dual-drug combination group (P < 0.05). The bile acid levels decreased significantly in both groups, but the decrease was more significant in the triple-drug group (P < 0.05). The triple-drug group also exhibited a greater reduction in the levels of certain liver enzymes and a lower incidence of adverse pregnancy outcomes compared to the dual-drug group (P < 0.05). CONCLUSION: Polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate effectively relieves pruritus and reduces bile acid levels and liver enzyme indices in patients with ICP, providing a positive impact on pregnancy outcome and a high safety profile. Further clinical trials are required prior to clinical application.

[Principles of treatment of different forms of alcoholic liver disease: A review].

The review considers the principles of treatment of various forms of alcoholic liver disease from the point of view of the evidence base and clinical recommendations. The main therapy for severe alcoholic hepatitis is systemic glucocorticosteroids, their effect on survival is increased by the addition of antioxidants (N-acetylcysteine, ademethionine). The effect of ademetionine on the life expectancy of patients with alcoholic cirrhosis of Child-Pugh class A and B has been proven. The treatment of patients with mild forms of alcoholic liver disease is not well developed, and the evidence base for most of the drugs used is modest.

THE EFFECT OF S-ADEMETIONINE ON PLASMA CITRULLINE LEVEL DURING CHEMOTHERAPY-INDUCED OXIDATIVE STRESS IN PATIENTS WITH CHRONIC LYMPHOPROLIFERATIVE DISORDERS.

OBJECTIVE: The aim: To investigate the effect of S-ademetionine on plasma citrulline level in patients with chronic lymphoproliferative disorders (CLPD) during chemotherapy-induced oxidative stress. PATIENTS AND METHODS: Materials and methods: 25 patients with CLPD were examined. Examinations were conducted twice: before chemotherapy (CT) and after 3 courses of CT. Several biochemical markers in the blood were determined: the activity of catalase, the level of plasma citrulline, the concentration of N-acetylneuraminic acid (NANA) and the concentration of substances that form a trimethine complex (TBARS) with 2-thiobarbituric acid. Patients were divided into groups: І (n=14) - patients who underwent only CT; ІІ (n=16) - patients who during CT received S-ademetionine, at a dose of 1000 mg/day intravenously for 10 days, then 500 mg twice a day for 20 days. ІІІ (n=20) -the control group of 20 practically healthy individuals. RESULTS: Results: Patients in both groups with CLPD had pre-existed mucosal injury that was characterized by 1.25 (p=0.0025) and 1.26 times (р=0.006) higher blood NANA concentration compared to the control group. The conduction of CT was associated with enterocytes dysfunction, which was characterized by 1,66 times (p=0,0002) lower plasma citrulline level in patients of group I compared to the initial examination. The infusion of S-ademetionine attenuated intestinal dysfunction that was associated with 1,23 times (p=0,0005) higher blood citrulline level after the CT as compared to group I. CONCLUSION: Conclusions: The infusion of S-ademetionine as adjuvant treatment in patients with CLPD provided effective prophylaxis of intestinal injury that was associated with higher blood citrulline level after the conduction of CT.

Pharmacokinetics and food impact assessment of ademetionine enteric-coated tablet as an endogenous substance drug in healthy Chinese volunteers.

WHAT IS KNOWN AND OBJECTIVES: Ademetionine 1,4-Butanedisulfonate (SAMe) enteric-coated tablets are widely used for treatment of pre-cirrhotic and cirrhotic intrahepatic cholestasis, as well as intrahepatic cholestasis of pregnancy (ICP), but incomplete clinical data and interference from endogenous substances pose numerous challenges for clinical trial of ademetionine. The objective of this study was to evaluate the pharmacokinetic profile of SAMe enteric-coated tablets and to assess its food impact and safety in healthy Chinese subjects. METHODS: A randomized, open-label, single-dose study was carried out to determine the pharmacokinetics of SAMe enteric-coated tablets administered in both fasted and postprandial conditions. Baseline collection and data adjustment were required to reduce the effect of endogenous substances. Relevant pharmacokinetic data from subjects administered the reference formulation will be disclosed and utilized in this thesis. RESULTS: Twenty-four subjects with a body mass index (BMI) of 19-24 kg/m2 were enrolled in the study and all completed the trial. The impact of food on the drug was noticeable, with faster absorption in the fasting group (Tmax , 4.50 ± 1.07 and 7.50 ± 1.58 for the fasting and postprandial groups, respectively) but higher exposure in the postprandial group (AUC0-inf , 4021.02 ± 3377.13 and 5087.28 ± 3539.26 for the fasting and postprandial groups, respectively). No serious adverse effects were observed in the fasted and postprandial conditions. WHAT IS NEW AND CONCLUSIONS: The pharmacokinetic profile of SAMe enteric-coated tablets in healthy Chinese subjects was partially complemented in this study. SAMe enteric-coated tablets showed promising safety in fasted and postprandial conditions. However, the impact of food on the drug was significant and might access to the absorption site and affect biochemical reactions.

[Mixed steatohepatitis: more questions than answers (part 2)].

In this review, we discussed the epidemiological and pathogenetic aspects of mixed steatohepatitis (SH), developed due to non-alcoholic fatty liver disease, metabolic associated fatty liver disease, drug-induced liver injury. We discussed the mechanisms of the mutually aggravating influence of etiological factors. Drugs can cause steatosis and SH, as well as contribute to the progressive course of existing SH, primarily of metabolic origin. The issues of interaction of pathogenetic factors, peculiarities of diagnostics and perspectives of pathogenetic and symptomatic treatment are considered. Therapy of mixed SH is based on avoidance of hepatotoxic drugs and lifestyle modification, medications with demonstrated efficacy (such as ademetionine) in certain SH might be used.

Pharmacokinetic study of a novel oral formulation of S-adenosylmethionine (MSI-195) in healthy subjects: dose escalation, food effect and comparison to a commercial nutritional supplement product.

BACKGROUND: A novel, high bioavailability oral, enteric coated tablet formulation of S-adenosylmethionine (MSI-195) has been developed for life science application. The present research reports on a Phase 1 study to (i) determine the safety of single doses of MSI-195 (ii) to determine the dose proportionality of MSI-195 at doses of 400, 800 and 1600 mg (iii) determine the pharmacokinetics of MSI-195 compared with a commercial reference product (SAM-e Complete™) over 24 h and (iv) to determine the effect of food on the pharmacokinetic profile of MSI-195 in human subjects. METHODS: This study was a pharmacokinetic and safety evaluation of MSI-195 and a commercial comparator broken into two stages. The first stage was an exploratory single ascending dose design of MSI-195 in 8 healthy normal male volunteers. The second stage was a single dose evaluation, targeting 26 male and female volunteers at set doses of MSI-195 and commercial comparator in a cross-over design followed by a food effect study on MSI-195. Plasma samples were collected and assayed for S-adenosylmethionine using a validated HPLC method with MS/MS detection. The main absorption and disposition parameters were calculated using a non-compartmental approach with a log-linear terminal phase assumption. Statistical analysis was based on an ANOVA model or t test as appropriate. RESULTS: MSI-195 was found to be generally well tolerated with an adverse event profile similar to the SAM-e Complete™ comparator product. The relative bioavailability of MSI-195 was approximately 2.8-fold higher than SAM-e Complete based on area under the curve (AUC) ratios for the two products and the MSI-195 formulation exposure based on AUC was found to be approximately dose proportional. There was a significant food effect for MSI-195 with a delayed time to maximum absorption Tmax, going from 4.5 h under fasted conditions to 13 h under fed conditions, and area under the curve with food reduced to 55% of that seen under fasting conditions. CONCLUSIONS: The overall conclusion was that MSI-195 was well tolerated and has markedly higher bioavailability compared with both the SAM-e Complete™ commercial product tested and, on a per mg basis, products reported in other literature. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04623034 . Retrospectively registered Nov 9, 2020.

Evaluation of the Protective Effect of Ademetionine, Cytoflavin, and Dihydroquercetetine on Blood Enzymes Activity in Rats Treated with High Doses of Sodium Valproate.

We evaluated the protective effect of ademetionine, cytoflavin, and dihydroquercetin on activity of serum enzymes in rats treated with high doses of sodium valproate for 28 days. Ademetionine and cytoflavin produced the greatest protective effect, the effect of dihydroquercetin was less pronounced. In rats treated with ademetionine, AST activity decreased as soon as on day 7 and remained at this level until the end of the experiment; ALT, alkaline phosphatase, and γ-glutamyl transferase activities decreased on days 21 and 28 of the study. Cytoflavin produced similar effects, the effect of dihydroquercetin was observed on days 21 and 28 for AST, ALT, alkaline phosphatase and on day 28 for γ-glutamyl transferase. These results substantiate the use of hepatoprotective drugs in case of long-term treatment with anticonvulsants in patients with epilepsy.

[Mixed steatohepatitis: more questions than answers (Part 1)].

The term steatohepatitis is used for a heterogeneous group of diseases of various etiologies, characterized by a similar morphological picture. Earlier the diagnosis of non-alcoholic fatty liver disease implied the exclusion of other causes of steatohepatitis, in recent years it has been suggested that a combination of various etiological variants of steatohepatitis is possible. The review considers the terminological, epidemiological and pathogenetic aspects of the most common combination: metabolic and alcoholic genesis, the issues of the mutual influence of etiopathogenetic factors and the identification of the predominant process. Issues of existing and prospective pathogenetic and symptomatic therapy are discussed in detail. Treatment of steatohepatitis is based on the elimination of known causal factors and lifestyle modification; therapy includes medications, that have been proven to be effective in certain types of steatohepatitis and symptomatic therapy as well.

Effects of Ursodeoxycholic Acid and Adenosine Methionine Combined with Polyene Phosphatidylcholine on Related Indicators of Pregnancy with Intrahepatic Cholestasis / 中国药房

OBJECTIVE:To explore the effects of ursodeoxycholic acid and adenosine methionine combined with polyene phos-phatidylcholine on related indicators of pregnancy with intrahepatic cholestasis(ICP). METHODS:Medical information of 90 ICP female were analyzed retrospectively and divided into control group(45 cases)and observation group(45 cases)according to drug use. Control group was given Ursodeoxycholic acid tablet 300 mg orally,3 times a day+Transmetil for injection 1 g added into 5%Glucose injection 250 mL intravenously,once a day. Observation group was additionally given Polyene phosphatidylcholine injec-tion 15 mL added into 5% Glucose injection 250 mL intravenously,once a day,on the basis of control group. Treatment course of 2 groups lasted for 2 weeks. The itching score,the levels of serum total bile acid(TBA),ALT and AST,pregnancy outcome and the occurrence of ADR were observed in 2 groups before and after treatment. RESULTS:Before treatment,there was no statistical significance in itching score,the levels of TBA,ALT and AST between 2 groups (P>0.05). After treatment,itching score,the levels of TBA,ALT and AST in 2 groups were significantly lower than before treatment,and the observation group was significant-ly lower than the control group,with statistical significance (P<0.05). The cesarean section rate,premature birth rate,fetal dis-tress rate and amniotic fluid rate of observation group were significantly lower than those of control group,with statistical signifi-cance(P<0.05). No obvious ADR was found in 2 groups during treatment. CONCLUSIONS:Ursodeoxycholic acid,ademetionine combined with polyene phosphatidylcholine can effectively alleviate itching symptoms,liver function and pregnancy outcome of ICP patients,with good safety.

Observation on the influence of ademetionine for the proteometabolism and fibrosis indexes of patients with chronic hepatitis B / 中国生化药物杂志

Objective To observe the influence of ademetionine for the proteometabolism and fibrosis indexes of patients with chronic hepatitis B.Methods110 patients with chronic hepatitis B in our hospital from January to December 2016 were randomly divided into control group(conventional treatment of hepatitis B group)55 cases and observation group(conventional treatment and ademetionine group)55 cases.The serum expression levels of proteometabolism and fibrosis indexes of two groups before the treatment and after the treatment were detected and compared.ResultsThe serum expression levels of proteometabolism and fibrosis indexes of two groups before the treatment were compared,there were no significant differences,while the serum expression levels of proteometabolism indexes of observation group after the treatment were all higher than those of control group,the serum expression levels of fibrosis indexes were all lower than those of control group,there were all significant differences(all P<0.05).ConclusionThe ademetionine can significantly improve the expression state of proteometabolism and fibrosis indexes of patients with chronic hepatitis B,so the application value for the patients with chronic hepatitis B is relatively higher.

Protective Effects of Ademetionine 1,4-Butanedisulfonate on Radiation Injury / 医药导报

Objective This study aimed to investigate the protective effects of ademetionine 1,4-butanedisulfonate (SMT) against radiation injuries.Methods ICR mice were randomly divided into 7 groups,including normal control,irradiation-only,SMT administration-only,low-,medium-and high-dosages (250,500,1 000 mg·kg-1) of SMT pre-irradiation and high-dose of SMT post-irradiation in experimental groups.Blood and immunological experiments,organs index experiment and 30-day''s survival experiment were carried out to observe the protective effects of SMT on peripheral blood and immune system,organ index and the whole body injuries.Results Compared with irradiation-only group (4.23±1.16) ×109·L-1,the number of nucleated cells in bone marrow was (11.20±4.63) ×109·L-1 in the high dose of SMT pre-irradiation.The difference between two groups was significant.Compared with irradiation-only group (19.25±9.36),the colony forming unit-spleen was (39.00±7.57) in the high-dose SMT pre-irradiation group,there was a significant difference between the two groups.The index of liver,spleen,kidney and pancreas were significantly higher than those of the irradiation-only group in SMT administration groups.The survival rate of mice treated with SMT was increased,especially for the high dose group (46% lifted) when compared with irradiation-only group.Conclusion SMT can protect mice from radiation injuries.

Effect of ademetionine on cytochrome P450 isoforms activity in rats.

Cocktail method was used to evaluate the influence of ademetionine on the activities of CYP450 isoforms CYP1A2, CYP2D6, CYP3A4, CYP2C19, CYP2C9 and CYP2B6, which were reflected by the changes of pharmacokinetic parameters of six specific probe drugs phenacetin, metroprolol, midazolam, omeprazole, tolbutamide and bupropion, respectively. The experimental rats were randomly divided into two group, control group and ademetionine group. The ademetionine group rats were given 50 mg/kg ademetionine by continuous oral administration for 7 days. The mixture of six probes was given to rats through oral administration and the blood samples were obtained at a series of time-points through the caudal vein. The concentrations of probe drugs in rat plasma were measured by UPLC-MS/MS. In the experiment for ademetionine and control group, there was statistical pharmacokinetics difference for phenacetin, metroprolol, midazolam, omeprazole, tolbutamide and bupropion. Continuous oral administration for 7 days could induce the activities of CYP450 isoforms CYP1A2 of rats, while it may inhibit the activities of CYP2D6, CYP3A4, CYP2C19 and CYP2C9.

Effect of ademetionine assisted therapy on serum transferrin, myocardial enzyme spectrum and bilirubin in icterus neonatorum / 中国生化药物杂志

Objective To investigate the effect of ademetionine assisted therapy on transferrin ( TRF) , myocardial enzyme spectrum and bilirubin in serum of patients with icterus neonatorum.Methods 86 cases of neonatal jaundice in the hospital were randomly divided into two groups.43 cases in control group were treated with conventional therapy, 43 cases in experimental group were treated by ademetionine.Serum transferrin, myocardial enzymes, serum total bilirubin levels and clinical effects were compared pre-treatment and post-weat ment.ResuIts Compared with control group, the TRF level of experimental group was higher (P<0.05), the level of Aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), and CK-MB in experimental group were lower (P<0.05), the total bile acid (TBA), total bilirubin (TBIL) and direct bilirubin (DBIL) in experimental group were lower (P<0.05).The total effective rate in experimental group was significantly higher than that in control group (χ2 =8.53, P<0.05).ConcIusion Ademetionine assisted therapy has a good clinical curative effect and could effectively reduce serum TRF, DBIL and myocardial enzyme spectrum level, which has important significance in the treatment of neonatal jaundice.

Efficacy of Ademetionine 1 ,4-Butanedisulfonate Enteric Coated Tables in the Treatment of Severe Intrahe-patic Cholestasis in Gestation Period and its Influence on Liver Function / 中国药师

Objective:To study the efficacy of ademetionine 1,4-butanedisulfonate enteric coated tables in the treatment of severe intrahepatic cholestasis in gestation period and its influence on liver function. Methods:From July 2013 to November 2014 in our hos-pital, 122 cases of severe intrahepatic cholestasis patients were divided into the observation group (61 cases) and the control group (61 cases) according to the admission order. The two groups of patients were given the conventional treatment, and the observation group was treated with ademetionine 1,4-butanedisulfonate enteric coated tables additionally. The clinical efficacy, pruritus, perinatal child and pregnancy outcomes were observed after the treatment. The liver function in the two groups before and after the treatment was com-pared. Results:Before the treatment, TB, TBA, DB, AST and ALT in the two groups showed no significant difference (P>0. 05). After the treatment, TB[(22.7 ±4.3) μmol·L-1], TBA [(14.3 ± 3.4) μmol·L-1], DB[(5.3 ± 0.8)μmol·L-1], AST [(73.2 ±13.2)U·L-1] and ALT [(82.5 ±10.3)U·L-1] in the observation group were significantly lower than those in the con-trol group[TB(28.3 ±4.8) μmol·L-1, TBA(21.5 ±5.2) μmol·L-1, DB(8.3 ±2.4) μmol·L-1, AST(245.1 ±38.3) U· L-1, ALT(221.4 ±37.4) U·L-1], and the difference was statistically significant(P<0.05). After the treatment, the total effec-tive rate in the observation group (96. 72%) was significantly higher than that in the control group (80. 33%), the degree of itching in the observation group was significantly lower than that in the control group, the perinatal children and pregnancy outcomes in the ob-servation group were significantly better than those in the control group, and the difference was statistically significant (P<0. 05). Conclusion:Ademetionine 1,4-butanedisulfonate enteric coated tables in the treatment of severe intrahepatic cholestasis during preg-nancy is effective with high security, which can significantly improve liver function, and is worthy of wide application.

Clinical efficacy of liver lesion with the treatment of reduced glutathione and ademetionine / 安徽医科大学学报

Clinical efficacy of liver lesion with the treatment of reduced glutathione and ademetionine was analyzed retrospectively. 83 patients were randomly divided into two groups based on the application of preventive hepatopro-tective drug. Control group was treated with reduced glutathione intravenous drip infusion once a day ( n =40 ) , while treatment group with reduced glutathione and ademetionine(Transmetil) once a day(n=43). After 12 days, the clinical efficacy of treatment group was better than that of control group. Total response rate was 95. 35% for treatment group, much better than that of control group(80. 00%). There was significant difference between two groups ( P<0.05 ) . Reduced glutathione and ademetionine are more effective in the treatment of chemotherapeutics-induced liver lesion than only with reduced glutathione.

Observation of the effect of biliary stenting combined with ademetionine on malignant obstructive jaundice / 中国基层医药

Objective To explore the effect of biliary stenting combined with ademetionine on malignant obstructive jaundice.Methods According to the digital table,60 patients of malignant obstructive jaundice were randomly divided into the control group and the observation group.The patients in the control group were treated with biliary stenting individually,and the observation group received biliary stenting and combined treatment with ademeotionine.The variety of liver function and C-reactive protein were observed.Results The liver function and index of Creactive protein of patients in the observation group were significantly superior to those in the control group (all P ＜0.01).Conclusion The treatment of malignant obstructive jaundice by biliary stenting combined with ademetionine is effective.The mechanism may be related to the effect of ademetionine on promoting cytothesis,glutathione synthesis and eliminating free-radicals.

Effects of S-ademetionine on proliferation of gastric cancer cell lines and methylation of c-myc and uPA genes / 中华消化杂志

Objective To investigate the impacts of S-ademetionine (SAM) on cell cycles,apoptosis and invasive capacity of gastric cancer cell lines,and its effects on methylation and expressions of c-myc and uPA.Methods MKN-28,SGC-7901 and MKN-45 cells were treated with gradient concentrations of SAM(0,2 and 4 mmol/L) for 72 hours.The changes of cell cycles and apoptosis were detected by flow eytometry,and invasion was detected by transwell assay.The expressions and methylations of c-myc and uPA were examined by RT-PCR and MSP,respectively.Results The cell apoptosis significantly increased and cell invasive capacity was restrained in three cell lines with increase of SAM concentration (all P values<0.01).In SGC-7901,the cell percentage of G0/G1 phase significantly increased [(74.53±2.49)% vs.(56.67±1.18)%,P<0.053,whereas the cell proliferation index (PI) decreased [(25.50±2.46)% vs.(43.33±1.18)%,P<0.05] in comparison with controls.The expressions of c-myc and uPA mRNA in SGC-7901,uPA mRNA in MKN-45 and in 4 mmol/L SAM treated MKN-28 significantly decreased.The methylations of c-myc gene in SGC-7901 and uPA gene in three cell lines were reversed after treated with SAM.Conclusions SAM reduces expressions of c-myc and uPA by reversing the methylations of c-myc in SGC-7901 and uPA in all three cell lines.However SAM,as methyl donor,can restrain the development and progression of tumor when hypomethylation widely presents in cancer.

Therapeutic Effecl of Combined Therapy of Hepatocyte Growth-Promoting Factor and Transmetil on Chronic Tepatitis B / 医学研究杂志

Objective To evaluate the therapeutic effect of combined therapy of hepatocyte growth-promoting factor(HGF)and ademetionine on complication with severe anringinous in chronic hepatitis B.Methods 160patients were randomly divided into treatment group A(54),control group B(53) and group C(53).The treatment group were treated with hepatocyte growth-promoting factor and Transmetil,the group B were treated with KUHUANG injection and HGF,the group C were treated with Potassium magnessium aspartape and HGF.The therapeutic courses were 30 days.Results The liver function(Tbil,AST,ALT,AKP,r-GGT),climical symptom and physical sign were compared before and after being treated.The recovery rates of liver function in treatment group were higher singnificantly than that of control group.The levels of liver function in treatment group after being treated is lower significantly than that of before(P

Mechanism of Ademetionine for Treating Hyper-unconjugated Bilirubinemia in Neonate Rats / 中国药房

OBJECTIVE:To investigate the efficacy and mechanism of ademetionine for treating hyper-unconjugated bilirubinemia in neonate rats.METHODS:The model of hyper-unconjugated bilirubinemia was established in 95 neonate SD rats by subcutaneously injection of phenylhydrazine hydrochloride,then the rats were randomly assigned to model control group(treated with normal saline),therapeutic control group(phenobarbital/nikethamide)and the therapeutic group(s-adenosyl-1-methionine)q.d for 7 days all by intraperitoneal injection.Blood samples were taken at different time for the analysis of the hepatic BUGT activity and serum bilirubin.RESULTS:In therapeutic control group compared with the model control group,the serum unconjugated bilirubin was lower,and the hepatic BUGT activity of therapeutic was higher(P