Delving into the Latest Updates on Adefovir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

9-(2-(phosphonomethoxy)ethyl)adenine, 9-(2-phosphonylmethoxyethyl)adenine, Adefovir (USAN/INN)

+ [6]

Target

HBV pol

Mechanism

HBV pol inhibitors(HBV DNA Polymerase inhibitors), Cell differentiation stimulants

Therapeutic Areas

Immune System DiseasesInfectious DiseasesDigestive System Disorders+ [1]

Active Indication-

Inactive Indication

Hepatitis BHIV Infections

Originator Organization

Rega Institute for Medical Research

Active Organization-

Inactive Organization

Rega Institute for Medical Research

Gilead Sciences, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

RegulationSpecial Review Project (CN)

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Structure

Molecular FormulaC8H12N5O4P

InChIKeySUPKOOSCJHTBAH-UHFFFAOYSA-N

CAS Registry106941-25-7

Lamivudine had been widely used for treatment-naïve chronic hepatitis B patients. However, development of antiviral resistance has been known as the major drawback: Incidence of lamivudine resistance was reported to be approximately 70% after 5 years (Lok AS et al, 2003). For the treatment of lamivudine resistance, adefovir has been widely used (Lok AS and McMahon B, 2009). However, switching to adefovir monotherapy was also reported to be at high risk of resistance, 25% at year 2 (Yeon JE et al, 2006). Recently, adding adefovir on lamivudine was shown to be superior to switching to adefovir monotherapy by decreasing the adefovir resistance (Rapti I et al, 2007, Lampertico P et al, 2007). However, combination of adefovir and lamivudine does not increase antiviral activity compared with adefovir monotherapy in patients with lamivudine resistance (Peters MG et al, 2004). As many patients are still viremic with the treatment of lamivudine and adefovir over 1 year, the investigators need more potent combination of the drugs. Telbivudine is a new nucleoside analogue with potent antiviral activity. The previous phase III study has shown the superiority of telbivudine over lamivudine in HBeAg positive and negative subjects (Lai CL et al, 2007). Therefore, telbivudine plus adefovir may be a better treatment option than lamivudine plus adefovir for the lamivudine-resistant chronic hepatitis B patients. No study assessing the efficacy of telbivudine plus adefovir has been conducted for these patients. The aim of this study is to evaluate the safety and efficacy of telbivudine plus adefovir compared with lamivudine plus adefovir in lamivudine resistant chronic hepatitis B patients at the end of 1 year follow-up,

Start Date01 May 2011

Sponsor / Collaborator

Korea University

100 Clinical Results associated with Adefovir

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100 Translational Medicine associated with Adefovir

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100 Patents (Medical) associated with Adefovir

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1,851

Literatures (Medical) associated with Adefovir

07 Aug 2024·Journal of the American Chemical Society

Regioselective Homolytic C²–H Borylation of Unprotected Adenosine and Adenine Derivatives via Minisci Reaction

Article

Author: Jiang, Yujie ; Zhou, Dazhi ; Que, Yingchuan ; Li, Zhiming ; Chen, Gang ; Zhou, Yutong ; Li, Yangyan ; Yang, Hui ; Butt, Madiha

A Minisci-type borylation of unprotected adenosine, adenine nucleotide, and adenosine analogues was successfully achieved through photocatalysis or thermal activation. Despite the challenges posed by the presence of two potential reactive sites (C² and C⁸) in the purine motif, the unique nucleophilic amine-ligated boryl radicals effortlessly achieved excellent C² site selectivity and simultaneously avoided the formation of multifunctionalized products. This protocol proved effective for the late-stage borylation of some important biomolecules as well as a few antiviral and antitumor drug molecules, such as AMP, cAMP, Vidarabine, Cordycepin, Tenofovir, Adefovir, GS-441524, etc. Theoretical calculations shed light on the site selectivity, revealing that the free energy barriers for the C²-Minisci addition are further lowered through the chelation of additive Mg²⁺ to N³ and furyl oxygen. This phenomenon has been confirmed by an IGMH analysis. Preliminary antitumor evaluation, derivation of the C²-borylated adenosine to other analogues with high-value functionalities, along with the CuAAC click reactions, suggest the potential application of this methodology in drug molecular optimization studies and chemical biology.

01 Jul 2024·Naunyn-Schmiedeberg's Archives of Pharmacology

Intravitreal ranibizumab injection is associated with an increased risk of chronic kidney disease: a population-based study in Taiwan

Article

Author: Chen, Chuan-Mu ; Lim, Paik Seong ; Yu, Teng-Shun ; Chuang, Wu-Lung ; Wu, Tsai-Kun ; Chang, Kuang-Hsi ; Chen, Chang-Hsu ; Tsai, Fuu-Jen

AbstractSystemic vascular endothelial growth factor (VEGF) blockade has been the top adjunctive chemotherapy since 1990. Anti-VEGF therapy has also been associated with worsened renal function in some patients. However, the association between patient outcomes and use of intravitreal VEGF inhibitors remains controversial. Thus, it is necessary to determine the action mechanism and long-term renal effects of ranibizumab. The National Health Insurance Research Database (NHIRD) is one of the largest global databases that are extensively used for epidemiological research. NHIRD contains the medical information of all insureds, such as inpatient, outpatient, emergency, and traditional Chinese medicine records. We selected subjects aged ≥ 20 years who recently administered ranibizumab for the ranibizumab cohort. Non-ranibizumab cohort consisted of subjects who did not receive ranibizumab, and the index date was a random date between 2008 and 2018. We excluded subjects with missing sex and age records and those in which the date of primary outcome was before the index date. The two cohorts were matched via 1:1 propensity score matching based on sex, age, index year, hypertension, diabetes mellitus, hyperlipidemia, stroke, coronary artery disease, alcoholism, chronic obstructive pulmonary disease, and age-related macular degeneration, retinal vein occlusion, and diabetic macular edema. Medical confounders were angiotensin I-converting enzyme inhibitors, statins, corticosteroids, VEGF inhibitors including bevacizumab and aflibercept, lithium, amphotericin B, adefovir, NSAIDS, cisplatin, and calcineurin inhibitors. Among 48,248 participants aged ≥ 20 years, 24,136 (50%) received ranibizumab (13,565 male [56.20%] and 10,571 female [43.80%]). Moreover, 24,136 participants who did not receive ranibizumab were matched by age, sex, comorbidities, and medications. Subjects who received ranibizumab exhibited a significantly higher risk of CKD than those who did not receive ranibizumab (adjusted hazard ratio = 1.88, 95% CI = 1.79–1.96). Our findings revealed that exposure to intravitreal ranibizumab is an independent risk factor for CKD. Therefore, physicians and ophthalmologists should make the patients aware of such a correlation to increase patient safety and decrease the CKD burden.

01 Jul 2024·European Journal of Clinical Pharmacology

Understanding adefovir pharmacokinetics as a component of a transporter phenotyping cocktail

Article

Author: Taubert, Max ; Bilal, Muhammad ; Fuhr, Uwe ; Dong, Qian ; Kinzig, Martina ; Dokos, Charalambos ; Scherf-Clavel, Oliver ; Sörgel, Fritz ; Chen, Chunli

AbstractPurposeAdefovir (as dipivoxil) was selected as a probe drug in a previous transporter cocktail phenotyping study to assess renal organic anion transporter 1 (OAT1), with renal clearance (CLR) as the primary parameter describing renal elimination. An approximately 20% higher systemic exposure of adefovir was observed when combined with other cocktail components (metformin, sitagliptin, pitavastatin, and digoxin) compared to sole administration. The present evaluation applied a population pharmacokinetic (popPK) modeling approach to describe adefovir pharmacokinetics as a cocktail component in more detail.MethodsData from 24 healthy subjects were reanalyzed. After establishing a base model, covariate effects, including the impact of co-administered drugs, were assessed using forward inclusion then backward elimination.ResultsA one-compartment model with first-order absorption (including lag time) and a combination of nonlinear renal and linear nonrenal elimination best described the data. A significantly higher apparent bioavailability (73.6% vs. 59.0%) and a lower apparent absorption rate constant (2.29 h−1 vs. 5.18 h−1) were identified in the combined period compared to the sole administration period, while no difference was seen in renal elimination. The population estimate for the Michaelis-Menten constant (Km) of the nonlinear renal elimination was 170 nmol/L, exceeding the observed range of adefovir plasma maximum concentration, while the maximum rate (Vmax) of nonlinear renal elimination was 2.40 µmol/h at the median absolute estimated glomerular filtration rate of 105 mL/min.ConclusionThe popPK modeling approach indicated that the co-administration primarily affected the apparent absorption and/or prodrug conversion of adefovir dipivoxil, resulting in the minor drug-drug interaction observed for adefovir as a victim. However, renal elimination remained unaffected. The high Km value suggests that assessing renal OAT1 activity by CLR has no relevant misspecification error with the cocktail doses used.

100 Deals associated with Adefovir

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External Link

KEGG	Wiki	ATC	Drug Bank
D02768	Adefovir	-	DB13868

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis B	Phase 2	-	Rega Institute for Medical Research	-
HIV Infections	Phase 2	US	Gilead Sciences, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01943799 (CTgov)	Phase 2	Hepatitis B, Chronic	178	OAV+telbivudine+tenofovir disoproxil fumarate+lamivudine+adefovir+entecavir (OAV Alone (Group A))	ctnrqgasyw(axejcyvcod) = cwzdwrzzbu rwhzxpdwor (mtlkzogfpb, bptepnabzh - dpgexdwlhj) View more	-	01 Nov 2019
				OAV+GS-4774 (OAV + GS-4774 2 YU (Group B))	ctnrqgasyw(axejcyvcod) = znwtypapus rwhzxpdwor (mtlkzogfpb, yecovlnosa - bjnxeckwmp) View more
NCT00023309 (CTgov)	Phase 2	Hepatitis B, Chronic	41	Lamivudine+adefovir (Lamivudine and Adefovir)	pighpgtwtg(tdpvdbjvmv) = evevgfgurm rfjnbcinui (tlagbilqjb, lluzzlqdaw - rjhzqaknut) View more	-	04 Apr 2013
				Adefovir alone (Adefovir)	pighpgtwtg(tdpvdbjvmv) = qnojehkwly rfjnbcinui (tlagbilqjb, amnvfbnqni - garwixyozd) View more