Adenine ; adverse effects ; analogs & derivatives ; therapeutic use ; Adult ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Infant, Newborn ; Male ; Organophosphonates ; adverse effects ; therapeutic use ; Paternal Exposure ; Pregnancy

Adenine ; adverse effects ; analogs & derivatives ; Fanconi Syndrome ; chemically induced ; Hepatitis B, Chronic ; drug therapy ; Humans ; Hypophosphatemia ; chemically induced ; Organophosphonates ; adverse effects ; Osteomalacia ; chemically induced

Adefovir dipivoxil (ADV) is an acyclic nucleotide phosphate analogue, currently used for anti-HBV therapy. A few cases of hypophosphatemia related to ADV were reviewed. We report two cases of chronic hepatitis B patients with the chief complaints of chest pain due to hypophosphatemia associated with ADV treatment.
Adenine ; adverse effects ; analogs & derivatives ; Chest Pain ; chemically induced ; Female ; Humans ; Hypophosphatemia ; chemically induced ; Male ; Middle Aged ; Organophosphonates ; adverse effects ; Young Adult

In therapy of chronic hepatitis B, there are new and exciting developments in antivirals such as nucleotide analogues. Adefovir dipivoxil is an oral prodrug of adefovir, a nucleotide analogue of adenosine monophosphate. This agent has a potent in vitro and in vivo effect against herpes virus, retroviruses, and hepadnaviruses. In the hepatitis B virus (HBV) setting, adefovir dipivoxil inhibits both the wild type and lamivudine-resistant HBV strains. The safety profile of adefovir dipivoxil 10 mg is excellent, but higher doses can produce renal tubular damage, particularly when the drug is used for prolonged therapy. Adefovir dipivoxil is an important new addition to the current first-line treatments for HBeAg positive and negative chronic hepatitis B, as well as being rescue therapy for lamivudine-resistant HBV strains. It is also licensed for use in adults with decompensated liver disease, as well as compensated liver disease where there is evidence of active viral replication, persistently elevated serum alanine aminotransferase levels and active liver inflammation and fibrosis. However, a longer follow-up is needed to establish the long term safety and efficacy of adefovir dipivoxil in patients with chronic HBV infection.
Adenine/adverse effects/*analogs & derivatives/*therapeutic use ; Antiviral Agents/adverse effects/*therapeutic use ; Hepatitis B, Chronic/*drug therapy ; Humans ; Liver Diseases/drug therapy ; *Phosphonic Acids

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans ; Antiretroviral Therapy, Highly Active/adverse effects* ; Anti-HIV Agents/adverse effects* ; HIV Infections/drug therapy* ; Tenofovir/therapeutic use* ; Retrospective Studies ; Emtricitabine/pharmacology* ; Adenine/therapeutic use* ; Lipids

BACKGROUNDTo assess the safety and tolerance of adefovir dipivoxil tablet in Chinese healthy volunteers.

METHODSTotally 42 healthy volunteers were enrolled in the study, 21 were female and 21 were male and their age ranged from 19 to 26 years. The subjects were randomly divided into 5, 10, 20, 40 and 60 mg dose-groups (6-10 subjects in each group) based on sex and weight, beginning with the 5 mg dose-group. Clinical symptoms, vital signs, electrocardiogram, routine blood test, routine urine test, prothrombin time and blood biochemical tests were recorded and evaluated.

RESULTSNo significant changes were found in clinical symptoms, vital signs and laboratory tests after dosing, except slight elevations of alanine aminotransferase in 2 subjects and bilirubin in 6 subjects observed and some gastrointestinal symptoms such as nausea and diarrhea found in 3 subjects, but the frequency and severity of all the adverse reactions were not found to be related to the dosages.

CONCLUSIONThe results showed that single oral dose of adefovir dipivoxil 60 mg or less was safe and tolerable.

Adenine ; administration & dosage ; adverse effects ; analogs & derivatives ; Administration, Oral ; Adult ; Antiviral Agents ; administration & dosage ; adverse effects ; Diarrhea ; chemically induced ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Nausea ; chemically induced ; Organophosphonates ; administration & dosage ; adverse effects ; Tablets ; Young Adult

OBJECTIVETo explore the efficacy and adverse effects of clofarabine for relapsed/refractory acute lymphoblastic leukemia in children.

METHODSTwenty-six pediatric patients with relapsed/refractory acute lymphoblastic leukemia were treated with clofarabine. There were 22 males and 4 females, with a mean age of 9.5 years (ranging from 4 to 17 years). They received clofarabine 52 mg/m2 intravenously over 2 hours daily for 5 days. Thirteen patients received two cycles and one patient received three cycles.

RESULTSIn the first cycle of clofarabine, complete remission was obtained in 11 children (42%) and partial remission was obtained in 7 children (27%). Eight children (31%) were considered unresponsive. In the second cycle, 11 (85%) of the 13 children obtained complete remission, 1 (8%) partial remission and 1 (8%) was unresponsive. One child received three cycles and obtained complete remission in each cycle. The common adverse events were myelosuppression, infection, liver dysfunction and gastrointestinal adverse reactions. There were no chemotherapy-related deaths.

CONCLUSIONSClofarabine is effective in the treatment of children with relapsed/refractory acute lymphoblastic leukemia and its adverse effects can be tolerated. Clofarabine could be a promising new treatment for relapsed/refractory acute lymphoblastic leukemia.

Adenine Nucleotides ; adverse effects ; therapeutic use ; Adolescent ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Arabinonucleosides ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Recurrence

A hyperuricemic rat model induced by adenine and ethambutol was established to investigate the anti-hyperuricemia activity and its mechanism of the flavonoid extract from saffron floral bio-residues. Sixty-seven SD rats were randomly divided into control group, model group, positive control group, and flavonoid extract groups(with 3 doses), respectively, and each group contained 11 or 12 rats. The hyperuricemic model was established by continuous oral administration of adenine(100 mg·kg~(-1)) and ethambutol(250 mg·kg~(-1)) for 7 days. At the same time, the positive control group was given allopurinol(20 mg·kg~(-1) per day) and the flavonoid extract groups were given the flavonoid extract at doses of 340, 170 and 85 mg·kg~(-1) per day, respectively. On day 8, rat serum, liver, kidney, and intestinal tissues were collected, and the levels of uric acid in serum and tissue, the xanthine oxidase activities and antioxi-dant activities in serum and liver were evaluated, and the kidney histopathology was explored. In addition, an untargeted serum metabolomics study was performed. According to the results, the flavonoid extract effectively reduced the uric acid levels in serum, kidney and ileum and inhibited the xanthine oxidase activities and elevated the antioxidant activities of serum and liver in hyperuricemic rat. At the same time, it reduced the levels of inflammation factors in kidney and protected renal function. Moreover, 68 differential metabolites of hyperuricemic rats were screened and most of which were lipids and amino acids. The flavonoid extract significantly retrieved the levels of differential metabolites in hyperuricemic rats, such as SM(d18:1/20:0), PC[18:0/18:2(92,12Z)], palmitic acid and citrulline, possibly through the following three pathways, i.e., arginine biosynthesis, glycine, serine and threonine metabolism, and histidine metabolism. To sum up, the flavonoid extract of saffron floral bio-residues lowered the uric acid level, increased the antioxidant activity, and alleviated inflammatory symptoms of hyperuricemic rats, which may be related to its inhibition of xanthine oxidase activity and regulation of serum lipids and amino acids metabolism.
Rats ; Animals ; Flavonoids/pharmacology* ; Uric Acid ; Crocus ; Xanthine Oxidase ; Ethambutol/adverse effects* ; Rats, Sprague-Dawley ; Hyperuricemia/drug therapy* ; Kidney ; Antioxidants/pharmacology* ; Plant Extracts/adverse effects* ; Amino Acids ; Adenine/adverse effects* ; Lipids

Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B (CHB). The objective of the present study was to compare the efficacy and safety of pegylated interferon (Peg-IFN) alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone (1.5 μg/kg once weekly) or Peg-IFN alpha-2b plus adefovir (10 mg daily) for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30 (36.7%) patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31 (25.8%) in the monotherapy group (P=0.36). In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group (76.7% vs. 29.0%, P<0.001). Thyroid dysfunction was more frequent in the combination group than in the monotherapy group (P<0.05). In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.
Adenine ; administration & dosage ; adverse effects ; analogs & derivatives ; Adolescent ; Adult ; Antiviral Agents ; administration & dosage ; adverse effects ; Drug Therapy, Combination ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; adverse effects ; Male ; Organophosphonates ; administration & dosage ; adverse effects ; Polyethylene Glycols ; administration & dosage ; adverse effects ; Prospective Studies ; Recombinant Proteins ; administration & dosage ; adverse effects

OBJECTIVETo investigate the regulatory effect of Yijing Fang (YJF) on adenine-induced infertility in rats with kidney deficiency.

METHODSSixty healthy Wistar male rats, aged 1.5 mo and weighing (180 +/- 10) g, were normally fed for a week, and then divided into five groups of equal number (blank control, infertile model, high-dose YJF, mid-dose YJF, and low-dose YJF) according to the body weight of the rats. The models were made by intragastric administration of 500 mg/ml adenine in gum arabic solution in the ratio of 1:10 at the dose of 1 ml per 100 g body weight per day for 10 days. YJF was given at 3.38 g, 1.69 g and 0.85 g per 100 g body weight per day to the rats in the high-, mid- and low-dose groups, respectively. After 48 days of treatment, we observed kidney deficiency-related changes in sperm concentration and motility, the levels of testosterone (T) and other hormones and the volumes of the testis, epididymis, seminal vesicle and prostate, and compared the indexes among different groups.

RESULTSYJF exhibited a significant regulatory effect on sperm concentration and motility, the T level and the indexes of the gonad and other accessory glands in the model rats (P < 0.05). After 48 days of treatment, sperm concentrations were (87.85 +/- 28.44), (7.11 +/- 2.15), (35.98 +/- 14.04), (32.65 +/- 11.80) and (33.51 +/- 13.26) x 10(6)/ml in the blank control, infertile model, high-dose YJF, mid-dose YJF, and low-dose YJF groups, respectively; sperm motilities were (52.79 +/- 16.43), (31.14 +/- 3.07), (45.88 +/- 16.97), (51.56 +/- 13.35) and (49.53 +/- 10.16)%; the T levels were (194.07 +/- 40.29), (61.27 +/- 13.70), (121.87 +/- 24.35), (127.44 +/- 19.38) and (127.81 +/- 20.28) nmol/L; the luteinizing hormone (LH) levels were (7.017 +/- 0.269), (6.117 +/- 0.894), (7.060 +/- 0.871), (7.156 +/- 0.937) and (6.967 +/- 0.778) IU/L; the testis volumes were (3.775 +/- 0.183), (2.865 +/- 0.258), (3.236 +/- 0.058), (3.457 +/- 0.066) and (3.398 +/- 0.091) g; the epididymis volumes were (1.119 +/- 0.116), (0.833 +/- 0.226), (1.124 +/- 0.104), (1.132 +/- 0.107) and (1.114 +/- 0.106) g; the prostate volumes were (176.75 +/- 427.09), (131.67 +/- 39.45), (178.70 +/- 37.97), (180.11 +/- 37.39) and (179.00 +/- 35.42) mg; and the body weights were (188.50 +/- 7.12), (189.92 +/- 6.67), (187.42 +/- 5.47), (189.17 +/- 6.19) and (188.75 +/- 6.12) g. Testis histopathology showed obvious injuries in the infertile models and different degrees of improvement in the three YJF groups, most evidently in the mid-dose group.

CONCLUSIONYifing Fang had an evident therapeutic effect on kidney deficiency-related infertility in adenine-induced rat models.

Adenine ; adverse effects ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Infertility, Male ; chemically induced ; drug therapy ; Male ; Phytotherapy ; Rats ; Rats, Wistar